2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T62b,Pharmacologic targeting of murine double minute 2 (MDM2) represents one of the most compelling strategies for therapeutic reactivation of wild-type p53 in hematologic malignancies. The MDM2-p53 autoregulatory loop is a central regulator of cellular stress responses, and in myeloid neoplasms-including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN)-p53 is frequently retained but functionally suppressed through MDM2 overexpression and oncogenic signaling, notably via JAK-STAT activation. Over the past decade, successive generations of MDM2 inhibitors have translated structural and mechanistic insights into clinical investigation, yielding critical lessons regarding dosing paradigms, hematologic toxicity, biomarker-driven patient selection, and mechanisms of resistance, including TP53-mutant clonal selection. While early phase III trials in AML were negative, recent studies in myelofibrosis demonstrate clinically meaningful spleen, symptom, and molecular responses, supporting disease-modifying potential in TP53-wild-type settings. Adaptive platform designs and rational combinations with JAK inhibitors, BCL-2 antagonists, and interferons have further refined therapeutic strategies. Emerging MDM2 degraders and next-generation agents aim to overcome feedback limitations and improve therapeutic index. This review integrates mechanistic foundations, clinical development, resistance biology, and future directions, highlighting how decades of basic science have reshaped p53 reactivation into a precision therapeutic paradigm in myeloid disease.31:T67a,Abstract Pharmacologic targeting of murine double minute 2 (MDM2) represents one of the most compelling strategies for therapeutic reactivation of wild-type p53 in hematologic malignancies. The MDM2–p53 autoregulatory loop is a central regulator of cellular stress responses, and in myeloid neoplasms—including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN)—p53 is frequently retained but functionally suppressed through MDM2 overexpression and oncogenic signaling, notably via JAK–STAT activation. Over the past decade, successive generations of MDM2 inhibitors have translated structural and mechanistic insights into clinical investigation, yielding critical lessons regarding dosing paradigms, hematologic toxicity, biomarker-driven patient selection, and mechanisms of resistance, including TP53-mutant clonal selection. While early phase III trials in AML were negative, recent studies in myelofibrosis demonstrate clinically meaningful spleen, symptom, and molecular responses, supporting disease-modifying potential in TP53–wild-type settings. Adaptive platform designs and rational combinations with JAK inhibitors, BCL-2 antagonists, and interferons have further refined therapeutic strategies. Emerging MDM2 degraders and next-generation agents aim to overcome feedback limitations and improve therapeutic index. This review integrates mechanistic foundations, clinical development, resistance biology, and future directions, highlighting how decades of basic science have reshaped p53 reactivation into a precision therapeutic paradigm in myeloid disease.32:T72d,In this study, we hypothesized that transcriptomic features among disease-driving hematopoietic stem and progenitor cells (HSPC) could improve current paradigms for risk stratification in myelofibrosis (MF). Therefore, we performed bulk RNA sequencing (RNA-seq) of blood from 358 patients with MF, split into training and test cohorts. Single-cell RNA-seq data from Lin-CD34+ MF HSPCs were used to guide the development of a prognostic model trained on the bulk RNA-seq data. A NanoString assay was used to validate our final model in 2 independent cohorts of patients with MF. We identified a 24-gene weighted-sum expression score (MPN24) that was prognostic of overall survival (OS). In 2 independent cohorts of 170 and 100 patients with MF, MPN24-high scoring patients had worse 5-year OS compared with MPN24-low scoring patients (25.5% vs 86.9%, hazard ratio [HR] = 9.81, P = 4.0e-11 and 23.5% vs 75.9%, HR, 6.40, P = 1.8e-7, respectively). MPN24-high was also associated with clinical, mutation and karyotypic features known to confer adverse risk in MF. The MPN24 score retained independent prognostic significance in multivariable analysis incorporating these covariates and existing risk stratification models including Dynamic International Prognostic Scoring System (DIPSS), DIPSS plus, Mutation-Enhanced International Prognostic Score System (MIPSS70), and MIPSS70 plus version 2.0, adding significant prognostic value to these risk stratification models (P = 1.6e-5, 4.0e-6, 1.5e-6, and 5.4e-4, respectively). The MPN24 score was particularly useful in improving risk-stratification of DIPSS-intermediate, and MIPSS70-intermediate and high-risk patients. MPN24 is an HSPC-derived gene expression score that is associated with OS independent of clinical and genomic prognostic variables and improves risk stratification in MF.33:T7bf, Abstract In this study, we hypothesized that transcriptomic features among disease-driving hematopoietic stem and progenitor cells (HSPC) could improve current paradigms for risk stratification in myelofibrosis (MF). Therefore, we performed bulk RNA sequencing (RNA-seq) of blood from 358 patients with MF, split into training and test cohorts. Single-cell RNA-seq data from Lin–CD34+ MF HSPCs were used to guide the development of a prognostic model trained on the bulk RNA-seq data. A NanoString assay was used to validate our final model in 2 independent cohorts of patients with MF. We identified a 24-gene weighted-sum expression score (MPN24) that was prognostic of overall survival (OS). In 2 independent cohorts of 170 and 100 patients with MF, MPN24-high scoring patients had worse 5-year OS compared with MPN24-low scoring patients (25.5% vs 86.9%, hazard ratio [HR] = 9.81, P = 4.0e−11 and 23.5% vs 75.9%, HR, 6.40, P = 1.8e−7, respectively). MPN24-high was also associated with clinical, mutation and karyotypic features known to confer adverse risk in MF. The MPN24 score retained independent prognostic significance in multivariable analysis incorporating these covariates and existing risk stratification models including Dynamic International Prognostic Scoring System (DIPSS), DIPSS plus, Mutation-Enhanced International Prognostic Score System (MIPSS70), and MIPSS70 plus version 2.0, adding significant prognostic value to these risk stratification models (P = 1.6e−5, 4.0e−6, 1.5e−6, and 5.4e−4, respectively). The MPN24 score was particularly useful in improving risk-stratification of DIPSS-intermediate, and MIPSS70-intermediate and high-risk patients. MPN24 is an HSPC-derived gene expression score that is associated with OS independent of clinical and genomic prognostic variables and improves risk stratification in MF. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Myelofibrosis: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Myelofibrosis (condition). Clinician-written summaries and actionable practice insights. 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Early-phase trial data for monoclonal antibodies are referenced but not fully detailed. Preclinical data for ADCs, bispecifics, and CAR-T remain to be validated in clinical settings.","practice_takeaway":"For patients with CALR-mutated MF or ET who respond poorly to hydroxyurea or ruxolitinib, mutant CALR-targeted monoclonal antibodies represent a promising disease-modifying option entering clinical trials—consider enrollment in early-phase studies. Peptide vaccines alone are unlikely to achieve hematologic or molecular remission based on current evidence."}},{"doi":"10.1200/jco-26-01827","pmid":"42531529","title":"Erratum: Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor–Naïve Myelofibrosis: Phase III SENTRY Trial","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-07-30T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-01827","source_score":61,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-04T06:22:23.221Z","updated_at":"2026-09-04T06:22:23.221Z","tags":[{"paper_doi":"10.1200/jco-26-01827","tag_type":"brand","value":"Jakafi","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"brand","value":"Xpovio","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"generic","value":"selinexor","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"modality","value":"XPO1 Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"study_design","value":"Phase III Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-26-01827","tag_type":"warning","value":"This paper is an erratum (correction notice) for the SENTRY Phase III trial, not the original trial report. No efficacy data, patient outcomes, or corrected values are provided in the source text. Summary fields requiring results or clinical detail have been left null accordingly. Clinicians should refer to the original SENTRY trial publication for full data.","value_numeric":null}],"summaries":{"what_studied":"This is an erratum notice for the Phase III SENTRY trial, which evaluated selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis patients."}},{"doi":"10.1158/2159-8290.cd-26-0410","pmid":"42008361","title":"Genomic Evolution of Myeloproliferative Neoplasms and Therapy-Associated Mutagenesis","journal_title":"Cancer Discovery","journal_issn":"2159-8274","published_at":"2026-07-30T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7619087/","source_score":65,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:06.327Z","updated_at":"2026-08-04T18:18:06.327Z","tags":[{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"condition","value":"Acute Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"condition","value":"Essential Thrombocythaemia","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"condition","value":"Myeloproliferative Neoplasms","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"generic","value":"azacitidine","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"generic","value":"hydroxycarbamide","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"modality","value":"Cytoreductive Agent","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"modality","value":"Hypomethylating Agent","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"sample_size","value":"n=30","value_numeric":30},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"study_design","value":"Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"warning","value":"Sample size of 30 patients is small; findings, particularly around therapy-associated mutagenesis, should be considered hypothesis-generating rather than definitive.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"warning","value":"The 203 whole-genomes from hematopoietic colonies used in phylogenetic analysis represents a separate analytical dataset embedded within the study — it is distinct from the 30-patient clinical cohort.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-26-0410","tag_type":"warning","value":"The full text page content was not extractable from the PDF; summary is based solely on the abstract and metadata. Specific subgroup sizes, statistical values, and detailed clinical outcomes could not be independently verified.","value_numeric":null}],"summaries":{"what_studied":"Longitudinal whole-genome and targeted sequencing in 30 patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), integrating clonal dynamics with 7,986 blood counts and clinical histories to characterize evolutionary patterns, disease progression, and therapy-associated mutagenesis.","key_result":"Distinct genomic evolutionary patterns separated stable from progressive disease: leukemic transformation arose via TP53 loss, stepwise driver mutation acquisition in complex clones, or emergence of independent leukemic clones, while stable disease showed long-term clonal equilibrium. Therapy-associated mutational signatures were identified — C>G mutations after azacitidine and T>A/T>G mutations after hydroxycarbamide — in blood but not skin. Phylogenetic analysis of 203 whole-genomes from hematopoietic colonies supported non-neoplastic (polyclonal) origins in triple-negative essential thrombocythaemia.","limitations":"Small cohort of 30 patients limits statistical power and generalizability. Full-text page content was not extractable, so granular clinical outcome data and subgroup sizes could not be verified. Causality of therapy-associated mutational signatures (vs. selection bias) cannot be fully established from observational sequencing alone.","practice_takeaway":"Genomic progression signals appear years before clinical transformation, supporting the value of serial molecular monitoring in MPN patients. Clinicians should be aware that hydroxycarbamide and azacitidine are associated with characteristic mutational signatures in blood cells, warranting further study of their long-term mutagenic potential."}},{"doi":"10.1038/s41408-026-01587-8","pmid":"42502117","title":"Selinexor for myelofibrosis or a drug in search of a disease?","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-07-25T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01587-8","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:17:55.665Z","updated_at":"2026-08-04T18:17:55.665Z","tags":[{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"brand","value":"Jakafi","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"brand","value":"Xpovio","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"generic","value":"selinexor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"modality","value":"XPO1 Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"sample_size","value":"n=353","value_numeric":353},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"study_design","value":"Editorial / Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"warning","value":"Level of evidence reflects the editorial study design, not the phase 3 SENTRY trial it discusses.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"warning","value":"Selinexor's brand name 'Xpovio' is inferred from known FDA approval context; not explicitly stated in the paper.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"warning","value":"The sample size tag reflects the largest trial discussed (SENTRY, n=353); the phase 2 single-agent study had only n=17 evaluable patients.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01587-8","tag_type":"warning","value":"This is an editorial/opinion piece, not a primary trial report; primary data for SENTRY (n=353) and other cited trials are summarized secondhand and not independently verifiable from this text alone.","value_numeric":null}],"summaries":{"practice_takeaway":"Selinexor plus ruxolitinib improves spleen responses but adds substantial toxicity without improving symptoms or anemia — clinicians should weigh this trade-off carefully, and the combination may have its clearest role as pre-transplant spleen debulking rather than routine first-line use.","what_studied":"This editorial reviews the clinical evidence for selinexor (an oral XPO1 inhibitor) in myelofibrosis, synthesizing data from a phase 2 single-agent study (n=17, JAKi-refractory/intolerant), a phase 1 combination study (n=24, JAKi-naïve), and the randomized phase 3 SENTRY trial (n=353, JAKi-naïve selinexor+ruxolitinib vs. placebo+ruxolitinib).","key_result":"In SENTRY, SVR35 at week 24 was 49.8% with selinexor+ruxolitinib vs. 28% with placebo+ruxolitinib, but the co-primary symptom endpoint (TSS improvement: −9.9 vs. −10.9) was not met, no anemia benefit was seen, and grade ≥3 adverse events were higher (70% vs. 50%), with nausea in 57% vs. 17% despite dual antiemetic prophylaxis.","limitations":"- Median treatment duration of only 11 months limits assessment of spleen response durability and survival benefit.\n- Early overall survival signal was based on few events (~12 months follow-up), unadjusted for risk, with survival curves converging beyond 21 months.\n- No comparator arm used optimal ruxolitinib dosing (20–25 mg twice daily), leaving uncertain whether add-on selinexor outperforms simply optimizing JAKi dose."}},{"doi":"10.1016/j.ccell.2026.06.008","pmid":"42425075","title":"Menin-dependent megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms","journal_title":"Cancer Cell","journal_issn":"1535-6108","published_at":"2026-07-09T00:00:00.000Z","url":"https://doi.org/10.1016/j.ccell.2026.06.008","source_score":35,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-15T13:26:08.781Z","updated_at":"2026-07-15T13:26:08.781Z","tags":[{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"brand","value":"Revumenib","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"condition","value":"Myeloproliferative Neoplasms","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"generic","value":"revumenib","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"modality","value":"Menin Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"study_design","value":"Preclinical Study (In Vitro and In Vivo)","value_numeric":null},{"paper_doi":"10.1016/j.ccell.2026.06.008","tag_type":"warning","value":"This is a preclinical study; no randomized clinical trial data in MPN patients are presented. The 'practice_changing' flag reflects the novelty of identifying menin as an MPN dependency, but clinical translation is still pending. The thrombocytopenia incidence (15–20%) is derived from leukemia trial data, not MPN populations. Sample size for human specimens is not specified in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This study investigated whether menin inhibition (via revumenib) reduces megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms (MPNs), using human CD34+ cultures, MPN patient specimens, and mouse models — including genetic knockout of MEN1 and its target MEF2C to confirm on-target effects.","key_result":"Revumenib showed potent anti-tumor activity in MPN models, synergized with ruxolitinib, suppressed megakaryopoiesis in primary MPN patient specimens both in vitro and in vivo, and caused only subtle effects in healthy mice; MEN1 and MEF2C knockout phenocopied drug effects.","limitations":"Results are largely preclinical (cell cultures and mouse models); clinical MPN patient data are limited to in vitro and in vivo specimen studies without a formal trial. The observed thrombocytopenia signal (15–20%) comes from heavily pre-treated leukemia patients, which may not reflect MPN populations.","practice_takeaway":"Menin inhibition with revumenib is a candidate therapy for MPNs, particularly in combination with ruxolitinib, but clinical trials in MPN patients are needed before practice change. Clinicians using revumenib for leukemia should monitor platelet counts, as megakaryocyte suppression appears to be an on-target drug effect."}},{"doi":"10.1182/blood.2025032360","pmid":"42378247","title":"TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-06-30T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032360","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:18.554Z","updated_at":"2026-07-14T13:24:18.554Z","tags":[{"paper_doi":"10.1182/blood.2025032360","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"brand","value":"Jakafi","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"generic","value":"navitoclax","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"modality","value":"BCL-2/BCL-XL Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"sample_size","value":"n=252","value_numeric":252},{"paper_doi":"10.1182/blood.2025032360","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"warning","value":"No proprietary brand name for navitoclax was mentioned in the source; none has been tagged.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"warning","value":"Overall survival data were not reported in this abstract; the survival benefit of the combination remains unknown at this follow-up.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032360","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied based on the significant SVR35 improvement, but regulatory approval of navitoclax for myelofibrosis was not confirmed in the source text—clinicians should verify current approval status before prescribing.","value_numeric":null}],"summaries":{"what_studied":"Phase 3 TRANSFORM-1 RCT (NCT04472598) evaluated navitoclax + ruxolitinib vs. placebo + ruxolitinib in 252 JAK-inhibitor-naïve adults with intermediate-2 or high-risk myelofibrosis, with a median follow-up of 20.3 months.","key_result":"SVR35 at Week 24 (primary endpoint) was achieved in 63.2% with NAV+RUX vs. 31.5% with PBO+RUX (P<0.0001); SVR35 at any time was 76.8% vs. 44.1%. TSS improvement at Week 24 was not significantly different (-10.2 vs. -11.6; P=0.2852). Grade 3/4 thrombocytopenia occurred in 54.0% vs. 19.2%, and Grade 3/4 neutropenia in 40.3% vs. 8.8%.","limitations":"- No significant difference in symptom burden (TSS) between arms, limiting the clinical benefit picture beyond spleen response.\n- Median follow-up of only 20.3 months; longer-term survival and disease-modification outcomes are not yet established.\n- Variant allele frequency reduction was an exploratory endpoint only, limiting conclusions about molecular benefit.","practice_takeaway":"NAV+RUX doubles the spleen volume response rate vs. ruxolitinib alone in frontline intermediate-2/high-risk myelofibrosis, but adds substantial hematologic toxicity—particularly thrombocytopenia and neutropenia—without a clear symptom benefit. Careful patient selection and proactive dose management are essential if this combination is used."}},{"doi":"10.1080/17474086.2026.2686813","pmid":"42316774","title":"Efficacy of pacritinib versus momelotinib in patients with thrombocytopenic myelofibrosis: a matching-adjusted indirect treatment comparison","journal_title":"Expert Review of Hematology","journal_issn":"1747-4086","published_at":"2026-06-30T00:00:00.000Z","url":"https://doi.org/10.1080/17474086.2026.2686813","source_score":8,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-31T13:37:03.972Z","updated_at":"2026-07-31T13:37:03.972Z","tags":[{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"condition","value":"Thrombocytopenia","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"generic","value":"momelotinib","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"generic","value":"pacritinib","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"study_design","value":"Matching-Adjusted Indirect Comparison (MAIC)","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"warning","value":"No sample size (total N after reweighting) was reported in the available abstract/results text, so a sample_size tag could not be assigned.","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"warning","value":"Study design label 'Matching-Adjusted Indirect Comparison' is a form of indirect treatment comparison, not a standard RCT; level of evidence assigned as 3 reflects the indirect comparative nature.","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"warning","value":"The full text provided is predominantly the INREBIC (fedratinib) U.S. Prescribing Information, not the MAIC study manuscript; summary data were drawn from the abstract and results sections only.","value_numeric":null},{"paper_doi":"10.1080/17474086.2026.2686813","tag_type":"warning","value":"The MAIC study concerns pacritinib vs. momelotinib, but the embedded full text is fedratinib prescribing information — clinicians should not conflate the study findings with fedratinib data.","value_numeric":null}],"summaries":{"what_studied":"This matching-adjusted indirect comparison (MAIC) evaluated pacritinib 200 mg BID (from PERSIST-2, platelet count 24–99 × 10⁹/L) versus momelotinib 200 mg QD (pooled from MOMENTUM and SIMPLIFY-1, platelet count <100 × 10⁹/L) in patients with thrombocytopenic myelofibrosis, assessing week-24 outcomes: TSS-50, SVR-35, RBC transfusion independence (RBC-TI), and overall survival (OS).","key_result":"All outcomes nominally favored pacritinib, but none reached statistical significance: TSS-50 OR 1.75 (95% CI 0.60–5.09), SVR-35 OR 1.40 (95% CI 0.32–6.04), RBC-TI OR 1.19 (95% CI 0.36–3.97), and OS HR 0.35 (95% CI 0.12–1.05). Notably, 76–81% of matched pacritinib patients had only moderate thrombocytopenia (platelets 50–99 × 10⁹/L).","limitations":"- MAIC methodology cannot fully replicate a head-to-head RCT; residual confounding from unmeasured variables is possible.\n- Most matched pacritinib patients had moderate (not severe) thrombocytopenia, limiting generalizability to patients with platelet counts <50 × 10⁹/L.\n- Wide confidence intervals reflect small effective sample sizes after reweighting, leaving all comparisons underpowered.","practice_takeaway":"In thrombocytopenic myelofibrosis, this indirect comparison shows a consistent but non-significant trend favoring pacritinib over momelotinib across symptom, spleen, transfusion, and survival endpoints. Clinicians should treat these results as hypothesis-generating rather than practice-changing, pending head-to-head trial data."}},{"doi":"10.1182/blood.2025032631","pmid":"42345360","title":"Galectin-1 Fuels Monocyte Hyperinflammation and Represents a Novel Therapeutic Target in Myeloproliferative Neoplasms","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-06-23T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032631","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-29T13:22:48.475Z","updated_at":"2026-06-29T13:22:48.475Z","tags":[{"paper_doi":"10.1182/blood.2025032631","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"brand","value":"OTX008","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"condition","value":"Essential Thrombocythemia","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"condition","value":"Myeloproliferative Neoplasm","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"condition","value":"Polycythemia Vera","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"generic","value":"galectin-1 inhibitor OTX008","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"modality","value":"Galectin Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"sample_size","value":"n=34","value_numeric":34},{"paper_doi":"10.1182/blood.2025032631","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"study_design","value":"Translational Study (scRNA-seq, CyTOF, In Vitro, In Vivo Mouse Model)","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"warning","value":"Sample size for human plasma ELISA (n=34 MPN, n=7 HI) is small; subgroup analyses by MPN subtype (PV n=8, ET n=13, MF n=13) are underpowered.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"warning","value":"Study design is predominantly preclinical and translational; no randomized clinical trial data are included — 'practice_changing' impact flag reflects novelty of therapeutic target, not clinical trial evidence.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"warning","value":"Study design tag reflects a multi-method translational study; no single canonical design label applies cleanly.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032631","tag_type":"warning","value":"TLR4–Gal-1 protein interaction is inferred by computational docking and co-immunoprecipitation only; direct structural confirmation is lacking.","value_numeric":null}],"summaries":{"what_studied":"This study investigated the role of galectin-1 (Gal-1/LGALS1) in monocyte-driven inflammation in myeloproliferative neoplasms (MPNs), using scRNA-seq, CyTOF, and functional assays in human MPN samples (n=34 patients) and a MPLW515L murine transplant model, with Lgals1 genetic knockout and pharmacological inhibition (OTX008).","key_result":"Gal-1 was elevated in MPN monocytes and plasma (vs. healthy controls, n=7 HI vs. n=34 MPN by ELISA); recombinant Gal-1 markedly increased inflammatory cytokine transcription and secretion in CD14+ MPN monocytes via TLR4/NF-κB signaling; Lgals1 knockout in the MPLW515L mouse model ameliorated leukocytosis and splenomegaly, and Gal-1 inhibition suppressed carrageenan-induced thrombosis and inflammation in vivo.","limitations":"- Murine MPLW515L transplant model may not fully recapitulate human MPN biology.\n- Human cohort is relatively small (n=34 MPN), limiting generalizability across MPN subtypes and mutational contexts.\n- Mechanistic TLR4–Gal-1 interaction is supported by computational docking and co-immunoprecipitation but lacks structural confirmation (e.g., crystallography).","practice_takeaway":"Gal-1 drives monocyte hyperinflammation in MPNs through TLR4/NF-κB signaling and may represent a druggable target; the Gal-1 inhibitor OTX008 warrants clinical investigation in MPN, particularly for patients with high monocyte counts or inflammatory burden."}},{"doi":"10.1182/bloodadvances.2025019152","pmid":"41779966","title":"Low serum cholesterol is a biomarker of advanced disease and poor outcomes in myeloproliferative neoplasms","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2025019152","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:46.502Z","updated_at":"2026-05-31T13:35:46.502Z","tags":[{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"condition","value":"Essential Thrombocythemia","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"condition","value":"Myelofibrosis","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"condition","value":"Myeloproliferative Neoplasm","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"condition","value":"Polycythemia Vera","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"generic","value":"hydroxyurea","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"modality","value":"Biomarker (Serum Cholesterol)","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"sample_size","value":"n=305","value_numeric":305},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"warning","value":"Median age was 69 years with 82.6% White patients from 3 academic centers in the US, which may limit generalizability to more diverse or community-based MPN populations.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"warning","value":"Patients on statins were excluded entirely — this improves cholesterol measurement validity but means findings cannot be applied to statin users, who represent a significant portion of the MPN population.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019152","tag_type":"warning","value":"The MF subgroup analysis (n=87) was likely underpowered; null findings in MF should not be interpreted as absence of effect. The ET/PV results drive the main conclusions.","value_numeric":null}],"summaries":{"what_studied":"This multicenter retrospective cohort study examined whether serum total cholesterol level (categorized as ≥150, 120–149, or <120 mg/dL) predicts MPN disease progression, major adverse cardiovascular events (MACE), and all-cause mortality in 305 adults with ET, PV, or MF who were not on statin therapy, over a median follow-up of 50.8 months.","key_result":"Total cholesterol <120 mg/dL was independently associated with 3× higher risk of MPN disease progression (aSHR 3.00; 95% CI 1.36–6.63), nearly 4× higher risk of heart failure hospitalization (aSHR 3.76; 95% CI 1.77–7.96), and ~2× higher all-cause mortality (aHR 1.87; 95% CI 1.06–3.30) vs. cholesterol ≥150 mg/dL; the association was strongest in ET/PV patients, not statistically significant in the MF subgroup (likely underpowered, n=87).","limitations":"- Retrospective design with selection bias: only MPN patients who underwent TTE were included, enriching for higher CV risk than the general MPN population.\n- Statin users were excluded, limiting generalizability and preventing assessment of statin effects on outcomes.\n- The MF subgroup was small (n=87), leaving MF-specific analyses underpowered.","practice_takeaway":"In MPN patients not on statins, a total cholesterol <120 mg/dL may signal advanced, high-risk disease and warrant closer monitoring for disease progression and heart failure — consider it a red-flag biomarker alongside spleen size and NLR. Clinicians should also continue to follow guideline-directed statin initiation given the elevated CVD risk in MPN, as prior data suggest potential benefit."}},{"doi":"10.1038/s41375-026-02975-6","pmid":"42086932","title":"MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms","journal_title":"Leukemia","journal_issn":"0887-6924","published_at":"2026-05-06T00:00:00.000Z","url":"https://doi.org/10.1038/s41375-026-02975-6","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-08","doi":"10.1038/s41375-026-02975-6","days":"7","issn":"0887-6924","rank":"8","field":"Clinical Medicine","score":"11","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1038/s41375-026-02975-6","title":"MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.","journal":"Leukemia","methods":"","results":"","abstract":"$30","keywords":[],"pubmed_id":"42086932","conclusions":"","publication_date":"2026-05-06T00:00:00"},"crossref":{"DOI":"10.1038/s41375-026-02975-6","URL":"https://doi.org/10.1038/s41375-026-02975-6","ISSN":["0887-6924","1476-5551"],"link":[{"URL":"https://www.nature.com/articles/s41375-026-02975-6.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41375-026-02975-6","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41375-026-02975-6.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms"],"author":[{"given":"Haifa K.","family":"Al-Ali","sequence":"first","affiliation":[]},{"given":"Sarah T.","family":"Heidel","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"Palandri","sequence":"additional","affiliation":[]},{"given":"Florian H.","family":"Heidel","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,5,5]]},"member":"297","prefix":"10.1038","source":"Crossref","volume":null,"created":{"date-time":"2026-05-05T06:46:01Z","timestamp":1777963561000,"date-parts":[[2026,5,5]]},"indexed":{"date-time":"2026-05-05T16:18:28Z","timestamp":1777997908706,"date-parts":[[2026,5,5]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000,"date-parts":[[2026,5,5]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000,"date-parts":[[2026,5,5]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.nature.com/articles/s41375-026-02975-6"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"14 February 2026"},{"name":"revised","group":{"name":"ArticleHistory","label":"Article History"},"label":"Revised","order":2,"value":"26 March 2026"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":3,"value":"20 April 2026"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":4,"value":"5 May 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":1,"value":"HAA: consulting or advisory role for BMS, Novartis, AbbVie, AOP Pharma, Blueprint, GSK, Otsuka, Stemline, MSD, Takeda; research funding from BMS, Incyte, Novartis; and travel support from Alexion and Abbvie. STH: none. FP: Consultancy and honoraria from NOVARTIS, GSK, BMS, INCYTE, SANOFI, TAKEDA, SOBI, AOP. FHH: honoraria from Novartis, Abbvie, CTI, BMS, MSD, GSK, AOP, Prelude, Silence, Telios, Kartos; consulting/advisory role for Novartis, Abbvie, CTI, BMS, MSD, GSK, AOP, Prelude, Silence, Telios, Kartos, Sumitomo, Janssen; and research funding from Novartis, BMS, CTI."}],"deposited":{"date-time":"2026-05-05T16:02:54Z","timestamp":1777996974000,"date-parts":[[2026,5,5]]},"issn-type":[{"type":"print","value":"0887-6924"},{"type":"electronic","value":"1476-5551"}],"published":{"date-parts":[[2026,5,5]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.1038/nrc991","key":"2975_CR1","year":"2003","issue":null,"author":"P Chene","volume":"3","first-page":"102","unstructured":"Chene P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. 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In ADORE, ruxolitinib+siremadlin achieved SVR35 in 30.4% at week 24 (60% in the 30 mg cohort), median spleen volume change −22.8% overall (−38.7% at 30 mg), TSS50 in 21.7%, and frequent grade ≥3 anemia (60.9%), thrombocytopenia (47.8%), and neutropenia (47.8%).","limitations":"Primary endpoint in BOREAS was not met (SVR35 p=0.08), and several efficacy and biomarker findings are from conference abstracts. ADORE was open‑label with small siremadlin cohorts (n=23) and early termination limited later platform parts; emergent low‑VAF TP53 mutations were observed but their clinical significance is uncertain.","practice_takeaway":"For TP53‑wild‑type myelofibrosis, MDM2 inhibition shows clinically meaningful spleen and symptom activity—especially with ruxolitinib add‑on—but cytopenias are common and require intermittent scheduling and close monitoring. 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Validation","value_numeric":null},{"paper_doi":"10.1182/blood.2025030094","tag_type":"warning","value":"Sample size sums development and validation cohorts; uniqueness of patients across cohorts is not confirmed in the abstract.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030094","tag_type":"warning","value":"Study design classification inferred from the abstract; prospective vs retrospective not specified.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030094","tag_type":"warning","value":"Study design label reflects a hybrid approach: retrospective model development with independent cohort validation using a locked NanoString assay—not a prospective RCT.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030094","tag_type":"warning","value":"The 'practice_changing' impact flag is applied based on the strength of the independent validation data; however, prospective clinical implementation has not yet been demonstrated.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030094","tag_type":"warning","value":"The total sample size of 628 reflects the two NanoString validation cohorts (n=170 + n=100) plus the RNA-seq training/test cohort (n=358); these cohorts overlap partially (PM-c1 patients contributed to both RNA-seq training and some NanoString benchmarking), so effective independent N is lower.","value_numeric":null}],"summaries":{"limitations":"- Cohorts are predominantly adult patients from academic centers; generalizability to community or non-Western populations is unclear.\n- Bone marrow fibrosis grade and some cytogenetic data were not uniformly available across all cohorts, limiting full covariate adjustment.\n- The NanoString assay was validated but not yet prospectively tested in a clinical workflow.","what_studied":"Bulk RNA-seq from 358 patients with myelofibrosis was used to build a hematopoietic stem/progenitor cell–derived 24‑gene score (MPN24), guided by single‑cell RNA‑seq from Lin‑CD34+ HSPCs, and validated by a NanoString assay in two independent cohorts (n=170; n=100).","key_result":"In two independent cohorts, MPN24‑high had worse 5‑year overall survival than MPN24‑low: 25.5% vs 86.9% (HR 9.81; P=4.0e‑11) and 23.5% vs 75.9% (HR 6.40; P=1.8e‑7). The score remained independently prognostic and added value beyond DIPSS, DIPSS plus, MIPSS70, and MIPSS70+ v2.0 (P=1.6e‑5, 4.0e‑6, 1.5e‑6, 5.4e‑4).","practice_takeaway":"Use the NanoString‑based MPN24 score alongside existing MF risk models to refine survival risk, particularly for DIPSS‑intermediate and MIPSS70‑intermediate/high categories."}}],"initialOffset":11,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Myelofibrosis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Myelofibrosis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Myelofibrosis"}}}]]

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