Saubia Fathima, Lior Rokach, Muhammad Yousuf, Priyansh Faldu, Ali Alsugair, Clifford Csizmar, Merry Nakhleh, Abhishek A. Mangaonkar, Animesh Pardanani, Luca Lanino, Alessia Campagna, Giulia Maggioni, Noushin Farnoud, Raajit Rampal, Kaaren K. Reichard, Rong He, Naseema Gangat, Mrinal M. Patnaik, Matteo G. Della Porta, Ayalew Tefferi
{"title":"CMML2AML: machine-learning discovery of co-mutations and specific single mutations predictive of blast transformation in chronic myelomonocytic leukemia","authors":"Saubia Fathima, Lior Rokach, Muhammad Yousuf, Priyansh Faldu, Ali Alsugair, Clifford Csizmar, Merry Nakhleh, Abhishek A. Mangaonkar, Animesh Pardanani, Luca Lanino, Alessia Campagna, Giulia Maggioni, Noushin Farnoud, Raajit Rampal, Kaaren K. Reichard, Rong He, Naseema Gangat, Mrinal M. Patnaik, Matteo G. Della Porta, Ayalew Tefferi","doi":"10.1038/s41408-026-01491-1","DOIUrl":"https://doi.org/10.1038/s41408-026-01491-1","url":null,"abstract":"Contemporary risk models in chronic myelomonocytic leukemia (CMML) focus on the prognostic relevance of individual rather than concurrent mutations. In the current study of 605 Mayo Clinic patients with CMML, we applied machine-learning algorithms in order to examine the influence of cooperative mutational interactions on blast transformation (BT). A hierarchical clustering algorithm was developed and tailored for patient stratification using survival outcomes and co-occurrence of genomic alterations. Five molecular clusters were identified with 3-year blast BT rates ranging from 0% to 100% (AUC at 3 years 0.78). A subsequent Cox regression analysis confirmed independent detrimental impact of specific mutations or their combinations including NPM1 (HR 26.7; p < 0.01), “NRAS + SETBP1” (HR 12.6; p < 0.01), “ASXL1 + BCOR” (HR 8.4; p < 0.01), “ASXL1 + RUNX1” (HR 2.2, p < 0.01), JAK2 (HR 2.1; p < 0.01), and “ASXL1 + TET2” (HR 1.7; p = 0.02) while “PHF6+wild-type ASXL1” (HR 5.61e−10; p < 0.01) had a favorable impact. Furthermore, compared to NPM1 wild-type cases, NPM1-mutated patients were less likely to have co-occurring mutations involving ASXL1 (0% vs. 43%, p < 0.01), RUNX1 (0% vs. 17%, p = 0.02), and SRSF2 (7% vs. 39%, p < 0.01) and were more likely DNMT3A (71% vs. 7%, p < 0.01). The prognostic relevance of “NRAS + SETBP1”, “ASXL1 + RUNX1”, NPM1 and BCOR was validated in an external cohort from Italy (N = 501). Taken together, these observations highlight i) the possibility of prognostic interaction of mutations in CMML that should be considered in the development of future risk models and ii) the distinct genotypic and prognostic characteristics of NPM1-mutated CMML.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"97 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655969","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}
Hamza Hashmi, Tara Sebastian, Sridevi Rajeeve, Tasmin Farzana, Ross S. Firestone, Eric M. Jurgens, Kevin C. Miller, Francesco Maura, Alexander M. Lesokhin, Carlyn R. Tan, Gunjan L. Shah, Neha Korde, Heather J. Landau, Maximillian Merz, Michael Scordo, Hani Hassoun, Kylee H. Maclachlan, Urvi A. Shah, Malin L. Hultcrantz, Andriy Derkach, David Nemirovsky, Sergio Giralt, Sham Mailankody, Saad Z. Usmani
{"title":"Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma","authors":"Hamza Hashmi, Tara Sebastian, Sridevi Rajeeve, Tasmin Farzana, Ross S. Firestone, Eric M. Jurgens, Kevin C. Miller, Francesco Maura, Alexander M. Lesokhin, Carlyn R. Tan, Gunjan L. Shah, Neha Korde, Heather J. Landau, Maximillian Merz, Michael Scordo, Hani Hassoun, Kylee H. Maclachlan, Urvi A. Shah, Malin L. Hultcrantz, Andriy Derkach, David Nemirovsky, Sergio Giralt, Sham Mailankody, Saad Z. Usmani","doi":"10.1038/s41408-026-01494-y","DOIUrl":"https://doi.org/10.1038/s41408-026-01494-y","url":null,"abstract":"While CAR T has shown superior efficacy in earlier line of therapy [1, 2] for functionally high-risk multiple myeloma (FHRMM), outcomes with its use in later lines (3+) for FHR disease remain unknown. We describe a single-center experience of FHRMM patients (pts), defined as those with progression of disease (POD) < 24 months of frontline therapy, receiving CAR T-cell therapy. Of the 208 pts treated with CAR T, 117 (56%) had FHR disease and had received median of 5 prior lines of therapy (LOT). FHR pts had higher rates of extramedullary disease (EMD) and progression within 12 months of transplant. Median PFS were 11 and 13 months (p = 0.15), and median OS were 34 and 55 months (p = 0.025) in the FHR and non-FHR groups, respectively. On multivariable analyses, EMD and high disease burden were associated with inferior OS. FHRMM pts receiving CAR T as late LOT had inferior survival outcomes compared to those with non-FHR disease, underscoring the poor prognostic impact of POD < 24 months from frontline therapy. This association was largely driven by active EMD and high disease burden at the time of CAR T, highlighting the potential benefit of utilizing CAR T as an early LOT for FHRMM.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"21 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655970","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":"Association of ciltacabtagene autoleucel with immune effector cell-associated enterocolitis: insights from a large national database.","authors":"Connor Frey,Mahyar Etminan,Hannah Cherniawsky","doi":"10.1038/s41408-026-01503-0","DOIUrl":"https://doi.org/10.1038/s41408-026-01503-0","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"33 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648998","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":"Aberrant glycosylation in hematologic malignancies: mechanisms, immune evasion, and therapeutic targeting.","authors":"Xiao Lu,Zhouying Song,Chunhui Wang,Bing Pan,Ziqi Xu,Zilong Wang,Hequn Wang,Xiaobo Wang,Bo Tang","doi":"10.1038/s41408-026-01493-z","DOIUrl":"https://doi.org/10.1038/s41408-026-01493-z","url":null,"abstract":"Hematologic malignancies are a group of malignant diseases originating from hematopoietic stem cells or the lymphatic system, mainly including leukemia, lymphoma, myeloma and so on. These diseases are characterized by their high heterogeneity, rapid disease progression and poor prognosis. Glycosylation is one of the most common post-translational modifications. In recent years, it has been found that abnormal glycosylation plays an important role in the genesis, development and treatment of hematologic malignancies. Aberrant glycosylation has been demonstrated to exert a significant influence on the progression of disease, impacting various biological processes including tumor cell signaling, the tumor microenvironment, cellular recognition, and immune evasion. This review synthesizes recent advances in how dysregulated glycosylation drives the biology of leukemia, lymphoma, myeloma, and other types of malignancies. Additionally, it discusses the potential value of glycosylation products that can be used as biomarkers for disease diagnosis and prognosis.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"94 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648894","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}
Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang
{"title":"Correction: Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations.","authors":"Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang","doi":"10.1038/s41408-026-01472-4","DOIUrl":"10.1038/s41408-026-01472-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Styrmir Hallsson, Ingibjorg Gunnarsdottir, Marianna Thordardottir, Sigrun Thorsteinsdottir, Johanna E. Torfadottir, Isleifur Olafsson, Ingunn Thorsteinsdottir, Jon Thorir Oskarsson, Andri Olafsson, Thorvardur J. Love, Sigurður Yngvi Kristinsson, Sæmundur Rögnvaldsson
{"title":"Dietary intake and the risk of monoclonal gammopathy of undetermined significance: results from the population-based iStopMM screening study","authors":"Styrmir Hallsson, Ingibjorg Gunnarsdottir, Marianna Thordardottir, Sigrun Thorsteinsdottir, Johanna E. Torfadottir, Isleifur Olafsson, Ingunn Thorsteinsdottir, Jon Thorir Oskarsson, Andri Olafsson, Thorvardur J. Love, Sigurður Yngvi Kristinsson, Sæmundur Rögnvaldsson","doi":"10.1038/s41408-026-01480-4","DOIUrl":"https://doi.org/10.1038/s41408-026-01480-4","url":null,"abstract":"Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM) and related disorders. Understanding the causes of MGUS is key to elucidating the causes of these malignancies. The association of MGUS and diet, including dietary patterns, remains unclear. We therefore assessed the relationship between diet and MGUS in the iStopMM a nationwide screening study for MGUS in Iceland where 75,422 individuals have been screened for MGUS. A food-frequency questionnaire was distributed to participants with 27,217 respondents, of whom 1,020 had MGUS at screening. Exposure was defined as dietary intake of specific dietary items and adherence to five dietary patterns identified through principal component analysis. Logistic regression was used to calculate odds ratios (OR) of having MGUS, adjusting for age, sex, physical activity, and education. No dietary patterns nor specific dietary components were associated with risk of MGUS overall. However, high consumption of dairy products was associated with increased odds (OR 2.01, 95% CI 1.16-3.65) of IgA MGUS, even after adjusting for multiple comparisons. These findings suggest that dietary habits are not a major risk factor for MGUS overall and therefore unlikely to be a major causative factor in the development of MM.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"38 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630950","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}
Amer M Zeidan,Valeria Santini,María Díez-Campelo,Michael R Savona,Mikkael A Sekeres,Yazan F Madanat,Pierre Fenaux,Azra Raza,Moshe Mittelman,Sylvain Thépot,Rena Buckstein,Ulrich Germing,David Valcárcel,Anna Jonášová,Sheetal Shah,Qi Xia,Libo Sun,Shyamala Navada,Tymara Berry,Uwe Platzbecker,Rami S Komrokji
{"title":"Association between treatment-emergent cytopenias and clinical responses to imetelstat in lower-risk myelodysplastic syndromes.","authors":"Amer M Zeidan,Valeria Santini,María Díez-Campelo,Michael R Savona,Mikkael A Sekeres,Yazan F Madanat,Pierre Fenaux,Azra Raza,Moshe Mittelman,Sylvain Thépot,Rena Buckstein,Ulrich Germing,David Valcárcel,Anna Jonášová,Sheetal Shah,Qi Xia,Libo Sun,Shyamala Navada,Tymara Berry,Uwe Platzbecker,Rami S Komrokji","doi":"10.1038/s41408-026-01501-2","DOIUrl":"https://doi.org/10.1038/s41408-026-01501-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"33 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630181","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}
Saubia Fathima, Lior Rokach, Nour Ghosoun, Mahsa Rezasoltani, Rimal Ilyas, Ali Alsugair, Kristen McCullough, Maymona Abdelmagid, Aref Al-Kali, Hassan B. Alkhateeb, Kebede H. Begna, Abhishek A. Mangaonkar, Aasiya Matin, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Mark R. Litzow, William Hogan, Mithun Shah, Mrinal M. Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Nathan Punwani, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Ayalew Tefferi, Naseema Gangat
{"title":"CPX-351 (Liposomal Cytarabine and Daunorubicin) versus venetoclax plus hypomethylating agent therapy in newly diagnosed acute myeloid leukemia: a retrospective comparison involving 600 Mayo Clinic patients","authors":"Saubia Fathima, Lior Rokach, Nour Ghosoun, Mahsa Rezasoltani, Rimal Ilyas, Ali Alsugair, Kristen McCullough, Maymona Abdelmagid, Aref Al-Kali, Hassan B. Alkhateeb, Kebede H. Begna, Abhishek A. Mangaonkar, Aasiya Matin, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Mark R. Litzow, William Hogan, Mithun Shah, Mrinal M. Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Nathan Punwani, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Ayalew Tefferi, Naseema Gangat","doi":"10.1038/s41408-026-01495-x","DOIUrl":"https://doi.org/10.1038/s41408-026-01495-x","url":null,"abstract":"The comparative value of liposomal cytarabine/daunorubicin (CPX-351) versus venetoclax plus a hypomethylating agent (Ven-HMA) in the frontline treatment of older adults with primary (de novo) or secondary acute myeloid leukemia (AML) remains uncertain. In the current study, we retrospectively examined outcomes of 600 patients with newly diagnosed AML treated with CPX-351 (N = 112) or Ven-HMA (N = 488). AML subtypes included de novo (N = 277, 46%), post-myelodysplastic syndrome (post-MDS, N = 114,19%), post-myeloproliferative neoplasm (post-MPN, N = 70, 12%), post-MDS/MPN (N = 36, 6%), and t-AML (N = 103, 17%). Patients receiving CPX-351 were younger (median 65 vs. 73 years; p < 0.01), predominantly female (50% vs. 38%; p = 0.02), more likely to have secondary AML (68% vs. 51%; p < 0.01), and less likely to harbor NPM1MUT (5% vs. 12%; p = 0.02). Rates of complete response with or without count recovery (CR/CRi) were comparable between CPX-351 and Ven-HMA (55% vs. 60%; p = 0.30), including AML with myelodysplasia-related gene mutations or cytogenetic abnormalities (AML-MR 60% vs. 63%; p = 0.70). Ven-HMA use was associated with fewer infectious complications (62% vs. 83%; p < 0.01) and yielded higher CR/CRi rates in males (60% vs. 45%; p = 0.04), de novo AML (68% vs. 50%; p = 0.03), and in the presence of STAG2MUT (86% vs. 44%; p = 0.02), or CEBPAMUT (88% vs. 50%; p = 0.03). Overall survival censored for transplant, was similar (median 10 vs. 13 months; p = 0.90), with Ven-HMA being superior in post-MDS AML (median 12 vs. 7 months; p = 0.02) and CPX-351 in the presence of SF3B1MUT (median not reached vs. 14 months; p < 0.01). Our findings suggest that Ven-HMA is as effective and less toxic than CPX-351 in newly diagnosed AML, including AML-MR, despite selection of younger, fitter patients for CPX-351.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"113 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619783","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}
Masooma Shifa Rana, Sebastian Fernandez-Pol, Alexandria Jensen, Vanna Hovanky, Arash Velayati, Jean S. Oak, Oscar Silva, Erik Ames, Lori S. Muffly, Bita Sahaf, Sally Arai, Vanessa E. Kennedy, Sushma Bharadwaj, David J. Iberri, Michaela Liedtke, Yasodha Natkunam, Parveen Shiraz, Wen-Kai Weng, Melody Smith, Matthew J. Frank, Crystal L. Mackall, Saurabh Dahiya, Lekha Mikkilineni, David B. Miklos, Hitomi Hosoya, Surbhi Sidana
{"title":"Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy","authors":"Masooma Shifa Rana, Sebastian Fernandez-Pol, Alexandria Jensen, Vanna Hovanky, Arash Velayati, Jean S. Oak, Oscar Silva, Erik Ames, Lori S. Muffly, Bita Sahaf, Sally Arai, Vanessa E. Kennedy, Sushma Bharadwaj, David J. Iberri, Michaela Liedtke, Yasodha Natkunam, Parveen Shiraz, Wen-Kai Weng, Melody Smith, Matthew J. Frank, Crystal L. Mackall, Saurabh Dahiya, Lekha Mikkilineni, David B. Miklos, Hitomi Hosoya, Surbhi Sidana","doi":"10.1038/s41408-026-01474-2","DOIUrl":"https://doi.org/10.1038/s41408-026-01474-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"114 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611941","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}
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