Leukemia最新文献

{"title":"HMGA1 and HMGA2: epigenetic regulators in myeloproliferative neoplasms and novel platelet transcriptomic biomarkers of myelofibrosis","authors":"Li Z. Luo,Leslie Cope,Zanshé Thompson,Anandi Krishnan,Yuze Du,Bailey West,Tania Jain,Jerry Spivak,Linda Resar","doi":"10.1038/s41375-026-03138-3","DOIUrl":"https://doi.org/10.1038/s41375-026-03138-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"26 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: spatial remodeling of bone marrow architecture defines tissue-state signatures of disease activity and therapeutic response in myelodysplastic neoplasms","authors":"Ryan Nachman,Aleksandra Kopacz,Caitlin Unkenholz,Jiani Chai,Arvin Ruiz,Itzel Valencia,Jeanne Jiang,Fabio Socciarelli,Jiwoon Park,Christopher E. Mason,Ling Zhang,David Sallman,Gail J. Roboz,Pinkal Desai,Justin Kaner,Joshua Fein,Monica Guzman,Neal Lindeman,Amy Chadburn,Madhu Ouseph,Paul Simonson,Julia Geyer,Giorgio Inghirami,Shahin Rafii,David Redmond,Sanjay S. Patel","doi":"10.1038/s41375-026-03090-2","DOIUrl":"https://doi.org/10.1038/s41375-026-03090-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"24 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations on TP53 variant classification for standardized reporting and interpretation","authors":"Kok-Siong Poon","doi":"10.1038/s41375-026-03136-5","DOIUrl":"https://doi.org/10.1038/s41375-026-03136-5","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"2022 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax-based therapy versus hypomethylating agents alone in unfit patients with newly diagnosed acute myeloid leukemia: a real-world study from the PETHEMA registry","authors":"Gaspar Aspas Requena, Eliana Aguiar, Joana Brioso, Rosa Ayala, Josefina Serrano López, Jorge Labrador Gómez, Eduardo Rodríguez-Arbolí, Mar Tormo, Teresa Bernal del Castillo, Olga Arce Fernández, Francisco Ibáñez Alís, Manuel Pérez Encinas, Carlos Rodríguez-Medina, Ágata Almela Gallego, Olga Salamero, José Luis López Lorenzo, Claudia Lucía Sossa Melo, María José Mela Osorio, Juan Miguel Bergua Burgues, Susana Vives, Aitor Abuín, María Dolores Madrigal, Cristina Gil, Alberto Giménez Conca, Marta Valero Núñez, José Mário Mariz, María-Ángeles Foncillas, Silvina Palmer, Marcela Espinoza, Bernardo Javier González González, María Carmen García Garay, Lara María Gómez García, Daniel García Belmonte, Ana Alfonso Piérola, Diana Marcela Cuervo Lozada, Carlos Varón, Ana Lisa Basquiera, Miguel López, María Lourdes Amador Barciela, María Solé Rodríguez, María Marta Rivas, Sandra Casal Marini, Alicia Roldán Pérez, María-Belén Vidriales, Raimundo García Boyero, Isabel Recio, María Luz Amigo, Kenny Gálvez, Pilar Lloret Madrid, Pau Montesinos","doi":"10.1038/s41375-026-03154-3","DOIUrl":"https://doi.org/10.1038/s41375-026-03154-3","url":null,"abstract":"Real-world comparisons of venetoclax (VEN)-based versus hypomethylating agent (HMA) monotherapy in unfit, newly diagnosed AML remain limited by short follow-up, low genomic testing, and inadequate statistical power. We conducted the largest comparative analysis to date from the PETHEMA registry, including 2610 patients (929 VEN-based, 1681 HMA). Composite complete remission was higher with VEN-based therapy (64.4% vs 20.0%; P < 0.001), and both 30-day (4.8% vs 7.5%; P = 0.011) and 60-day mortality (9.7% vs 15.7%; P < 0.001) were significantly lower. Median overall survival was 11.4 versus 8.2 months (HR, 0.66; 95% CI, 0.60–0.73; P < 0.001), consistent with that of VIALE-A (HR, 0.66) despite a broader cohort (ECOG 3–4, 4.7%; secondary AML, 42.5%; adverse-risk cytogenetics, 36.5%). The benefit was confirmed by propensity score matching (HR, 0.66), era-restricted analysis (HR, 0.71), and multivariable Cox regression. A molecular gradient of benefit emerged—greatest in IDH2 (HR, 0.43), NPM1 (0.46), FLT3-ITD (0.48), IDH1 (0.55), and favorable-risk cytogenetics (0.25). In TP53-mutated AML, OS improved significantly (HR, 0.70) but remained dismal (7.0 vs 3.7 months); no benefit was observed in AML arising from antecedent MDS or MPN. These findings confirm and extend VIALE-A, refining patient selection for VEN-based therapy in routine practice.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic myeloid leukemia in a global context: confirmatory findings and novel discoveries from a refined Japanese Cohort","authors":"Mai Fujita,Hiroshi Ureshino,Shinya Kimura","doi":"10.1038/s41375-026-03155-2","DOIUrl":"https://doi.org/10.1038/s41375-026-03155-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"480 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity to ATR–CHK1 pathway inhibition in MDS/AML is enhanced by SRSF2 mutations and reduced by RUNX1 loss","authors":"Samuli Eldfors, Sumit Rai, Vineet Sharma, Tareq Hossan, Claudia Cabrera Pastrana, Amy Bertino, Angelique Gilbert, Sridhar Nonavinkere Srivatsan, Kimmo Porkka, Matthew J. Walter, Timothy A. Graubert","doi":"10.1038/s41375-026-03142-7","DOIUrl":"https://doi.org/10.1038/s41375-026-03142-7","url":null,"abstract":"SRSF2 mutations occur in 5–15% of acute myeloid leukemia (AML) and ~15% of myelodysplastic neoplasms (MDS), are enriched in elderly/secondary AML, and lack mutation-directed therapy. We aimed to identify vulnerabilities in MDS/AML with SRSF2 mutations. Ex vivo drug-sensitivity testing of bone marrow cells from AML patients and controls showed that SRSF2-mutant cells are sensitive to CHK1 and WEE1 inhibitors. To test causality, we engineered isogenic K562 cell line clones expressing SRSF2P95H/L/R mutations. RNA sequencing confirmed splicing aberrations characteristic of MDS/AML in these clones. We found that SRSF2P95H/L/R sensitizes cells to ATR–CHK1–WEE1 inhibition. Bone marrow progenitors from Srsf2P95H knock-in mice showed heightened sensitivity to CHK1 inhibition, corroborating the human SRSF2-mutant data. U2af1S34F knock-in mouse progenitors extended this vulnerability to another spliceosome-mutant context. In contrast, RUNX1 mutations were linked to resistance to CHK1 and WEE1 inhibition in SRSF2-mutant AML samples. Runx1 disruption also caused resistance to CHK1 inhibitors in knock-in mouse progenitors harboring Srsf2P95H or U2af1S34F, indicating that RUNX1 loss of function is a mechanism of resistance. In conclusion, SRSF2 and U2AF1 mutations are biomarkers of sensitivity to ATR–CHK1 pathway inhibitors, while RUNX1 mutations cause resistance in splicing factor-mutant cells. These biomarkers can support patient stratification in MDS/AML.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"8 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAIA frailty subgroup analysis: long-term follow-up with daratumumab plus lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma","authors":"Thierry Facon, Gordon Cook, Saad Z. Usmani, Cyrille Hulin, Shaji Kumar, Cyrille Touzeau, Nizar J. Bahlis, Supratik Basu, Hartmut Goldschmidt, Hang Quach, Mohamad Mohty, Christopher P. Venner, Katja Weisel, Noopur Raje, Salomon Manier, Mai Ngo, Marjohn Armoon, Kasey Bolyard, Fredrik Borgsten, Robin Carson, Sonja Zweegman","doi":"10.1038/s41375-026-03128-5","DOIUrl":"https://doi.org/10.1038/s41375-026-03128-5","url":null,"abstract":"In MAIA (Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus Rd in transplant-ineligible newly diagnosed multiple myeloma (NDMM). Here, we report an updated subgroup analysis by frailty status. We retrospectively performed frailty assessments using age, Charlson Comorbidity Index, and baseline Eastern Cooperative Oncology Group performance status score; patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. After a 64.5-month median follow-up, OS benefit of D-Rd versus Rd was maintained in the non-frail subgroup (median, not reached [NR] vs 69.8 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37–0.76; P = 0.0004); the OS HR point estimate favored D-Rd versus Rd in the frail subgroup (NR vs 50.4 months; HR, 0.79; 95% CI, 0.58–1.06; P = 0.1128). Improved PFS and rates of complete response or better and minimal residual disease negativity (10–5) were observed with D-Rd versus Rd across frailty subgroups. Duration of therapy was consistently longer with D-Rd versus Rd, highlighting the improved disease control and long-term tolerability of daratumumab in frail patients. These long-term data, although limited by the retrospective assessment of frailty using baseline characteristics, continue to support the therapeutic benefit of D-Rd in terms of improved PFS and higher rates of deep responses in transplant-ineligible NDMM, regardless of frailty status.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KT-253, a highly potent and selective MDM2 protein degrader, eliminates malignant myelofibrosis stem/progenitor cells","authors":"Min Lu, Lijuan Xia, Yogesh Chutake, Joyoti Dey, Ronald Hoffman","doi":"10.1038/s41375-026-03163-2","DOIUrl":"https://doi.org/10.1038/s41375-026-03163-2","url":null,"abstract":"Approximately 96% of myelofibrosis (MF) patients express wild-type (WT) p53. MF hematopoietic stem/progenitor cells (HSPCs) overexpress MDM2 that degrades WTp53, thereby supporting MF HSPC survival. Although MDM2 small-molecule inhibitors (SMIs) are clinically effective, their benefit is compromised by an inability to sufficiently deplete MF HSPCs. KT-253 degrades MDM2 and overcomes the p53-dependent feedback loop that restores MDM2 levels observed with the use of MDM2 SMIs such as AMG-232. We evaluated the effects of KT-253 using MPN cell lines, primary MF CD34+ cells, and a mouse xenograft model. KT-253 activity was correlated with activation of the p53 pathway and upregulation of p53 downstream genes, including p21, NOXA, and PUMA in WTp53 UKE-1 cells but not p53 mutant cells. KT-253 treatment induced apoptosis of primary MF CD34+ cells at a tenfold lower concentration than AMG-232 and prevented the upregulation of MDM2 seen with AMG-232. Low doses of KT-253 reduced total MF colony and JAK2V617F+ colony numbers to a far greater extent than log-higher doses of AMG-232 (60% and 71% versus 20% and 10%, respectively). Mouse xenograft studies indicated that KT-253 more effectively depleted JAK2V617F+ MF marrow-repopulating cells. These findings support the further clinical evaluation of MDM2 degraders for the treatment of MF patients.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurable residual disease-guided, fixed-duration, potentially definitive therapy for standard risk newly diagnosed multiple myeloma","authors":"Bhagirathbhai R. Dholaria, Eva Medvedova, Gayathri Ravi, Binod Dhakal, Natalie S. Callander, Kelly N. Godby, Susan Bal, Timothy Schmidt, Rebecca W. Silbermann, Luciano J. Costa","doi":"10.1038/s41375-026-03162-3","DOIUrl":"https://doi.org/10.1038/s41375-026-03162-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant hematopoietic growth factors in acute myeloid leukemia","authors":"Margery Gang,Robert Peter Gale,Roland B. Walter","doi":"10.1038/s41375-026-03158-z","DOIUrl":"https://doi.org/10.1038/s41375-026-03158-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}