Leukemia最新文献_第3页

Are real world data real world data? 真实世界的数据是真实世界的数据吗？

IF 13.4 1区医学

Leukemia Pub Date : 2025-09-11 DOI: 10.1038/s41375-025-02751-y

Robert Peter Gale, Andreas Hochhaus

引用次数: 0

Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival 急性髓系白血病细胞表达高水平的雄激素受体，但不依赖于雄激素信号来生存

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-11 DOI: 10.1038/s41375-025-02752-x

Farideh Miraki-Moud, Linda Ariza-McNaughton, Thinzar KoKo, Jad Othman, Randal Stronge, Johann de Bono, Nigel Russell, Ian Thomas, Amanda Gilkes, Alan Burnett, Leandro Rodrigues Santiago, Fay Cafferty, Leo Taussig, Allan Thornhill, Simon O’Connor, Dominique Bonnet, David C. Taussig

{"title":"Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival","authors":"Farideh Miraki-Moud, Linda Ariza-McNaughton, Thinzar KoKo, Jad Othman, Randal Stronge, Johann de Bono, Nigel Russell, Ian Thomas, Amanda Gilkes, Alan Burnett, Leandro Rodrigues Santiago, Fay Cafferty, Leo Taussig, Allan Thornhill, Simon O’Connor, Dominique Bonnet, David C. Taussig","doi":"10.1038/s41375-025-02752-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02752-x","url":null,"abstract":"Male sex is associated with worse outcome in acute myeloid leukemia (AML) in many studies. We analyzed the survival of 4281 patients treated with intensive chemotherapy in the AML17 and AML19 trials based on sex. Men had a significantly lower remission rate than women. Men had a higher incidence of adverse cytogenetic features and a lower incidence of the relatively favorable NPM1 mutation. However, male sex was an independent risk factor for survival in multi-variate analysis. We hypothesized that androgen signaling in men could worsen outcomes by protecting AML cells from chemotherapy. We demonstrated high levels of androgen receptor (AR) expression in AML across cytogenetic risk groups. We showed the AR expression was induced by IL-6 signaling in vitro and correlates with poor overall survival. Androgens had no effect on survival of primary AML cells in vitro, nor did they impact gene expression. Androgens did not protect AML cells against chemotherapy either in vitro or in vivo. Similar results were observed with estrogen signaling through estrogen receptor in vitro in AML cells. In conclusion, targeting the androgen pathway may not be a promising clinical strategy and sex hormone signaling in AML cells does not explain the poorer outcomes of men.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"13 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032045","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}

引用次数: 0

Estimating the burden of chronic stress through allostatic load in patients with chronic myeloid leukemia 通过适应负荷估算慢性髓性白血病患者的慢性应激负担

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-11 DOI: 10.1038/s41375-025-02763-8

Marisol Miranda-Galvis, Kellen C. Tjioe, Muhannad Sharara, McKenzie Maloney, Amany R. Keruakous, Anand Jillella, Vamsi Kota, Avirup Guha, Jorge E. Cortes

{"title":"Estimating the burden of chronic stress through allostatic load in patients with chronic myeloid leukemia","authors":"Marisol Miranda-Galvis, Kellen C. Tjioe, Muhannad Sharara, McKenzie Maloney, Amany R. Keruakous, Anand Jillella, Vamsi Kota, Avirup Guha, Jorge E. Cortes","doi":"10.1038/s41375-025-02763-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02763-8","url":null,"abstract":"Despite advances in tyrosine kinase inhibitor (TKI) therapy, outcomes in chronic myeloid leukemia remain (CML) highly variable, underscoring the need to explore determinants beyond conventional clinical indicators. This study examined the relationship between allostatic load (AL), a biomarker-based index of cumulative chronic stress, social determinants of health (SDH), and treatment outcomes. In a retrospective cohort of 194 patients, AL was calculated using 23 biomarkers spanning cardiovascular, metabolic, hematologic, renal, and hepatic systems. Higher AL was associated with adverse SDH and behavioral factors, including greater extreme poverty (p = 0.02), limited transportation access (p = 0.02), reliance on public health coverage (p = 0.03), and physical inactivity (p = 0.05). Each unit increase in AL reduced the odds of achieving optimal molecular response by 18% (p = 0.02). All 11 disease progressions to advanced CML and all 9 deaths occurred in the high AL group, who also had higher rates of composite adverse events, including loss of molecular response, TKI failure, disease progression, and mortality (p = 0.03). These findings position AL as a promising integrative biomarker to identify high-risk patients facing combined physiological stress burden and social disadvantage, enabling oncology practices to refine risk stratification and implement personalized, multidisciplinary interventions.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"53 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032120","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}

引用次数: 0

Plasmapheresis facilitates soluble BCMA clearance and contributes to reversing primary resistance to anti-BCMA immunotherapy in multiple myeloma 血浆置换促进可溶性BCMA清除，有助于逆转多发性骨髓瘤抗BCMA免疫治疗的原发性耐药

IF 13.4 1区医学

Leukemia Pub Date : 2025-09-10 DOI: 10.1038/s41375-025-02757-6

Sven Neubert, Umair Munawar, Julia Mersi, Julia Noderer, Silvia Nerreter, Shilpa Kurian, Seungbin Han, Christina Verbruggen, Emma Besant, Nina Rein, Max Köppel, Johanna Lehmann, Tabea Köhler, Hannah Labinsky, Sigrun Häusl, Yoko Tamamushi, Xiang Zhou, Jule Pinter, Anna Laura Herzog, Kai Lopau, Elion Hoxha, Christoph Rummelt, Elena Gerhard-Hartmann, Andreas Rosenwald, Torsten Steinbrunn, Thomas Nerreter, Michael Hudecek, Hermann Einsele, Leo Rasche, K. Martin Kortüm, Johannes M. Waldschmidt

引用次数: 0

A three-dimensional ex vivo model recapitulates in vivo features and drug resistance phenotypes in childhood acute lymphoblastic leukemia 一个三维离体模型概括了儿童急性淋巴细胞白血病的体内特征和耐药表型

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-10 DOI: 10.1038/s41375-025-02739-8

Magdalini Kanari, Iria Jimenez Garcia, Fabio D. Steffen, Lisa A. Krattiger, Charles Bataclan, Wangjie Liu, Benjamin R. Simona, Bart Deplancke, Olaia Naveiras, Martin Ehrbar, Beat Bornhauser, Jean-Pierre Bourquin

{"title":"A three-dimensional ex vivo model recapitulates in vivo features and drug resistance phenotypes in childhood acute lymphoblastic leukemia","authors":"Magdalini Kanari, Iria Jimenez Garcia, Fabio D. Steffen, Lisa A. Krattiger, Charles Bataclan, Wangjie Liu, Benjamin R. Simona, Bart Deplancke, Olaia Naveiras, Martin Ehrbar, Beat Bornhauser, Jean-Pierre Bourquin","doi":"10.1038/s41375-025-02739-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02739-8","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) preferentially localizes in the bone marrow (BM) and displays recurrent patterns of medullary and extra-medullary involvement. Leukemic cells exploit their niche for propagation and survive selective pressure by chemotherapy in the BM microenvironment, suggesting the existence of protective mechanisms. Here, we established a three-dimensional (3D) BM mimic with human mesenchymal stromal cells and endothelial cells that resemble vasculature-like structures to explore the interdependence of leukemic cells with their microenvironment. This model recapitulates recurrent topologic differences between B-cell and T-cell precursor ALL, whereby B-ALL interacts more closely with the mesenchymal compartment. Migration versatility was found to be associated with subtype, consistent with increased motility observed in T-ALL in vivo. Single-cell RNA signatures revealed similarities to profiles from in vivo patient derived xenografts, suggesting relevant states ex vivo. Furthermore, enhanced migration, adherence and cell cycle heterogeneity was visualized in our co-culture model. Finally, drug response experiments in this 3D model confirm clinically relevant sensitivity and resistance patterns that reflect specific disease phenotypes and may provide a broader dynamic range for drug response testing.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"13 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025304","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}

引用次数: 0

PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias PML: RARα+骨髓细胞显示代谢改变，可靶向治疗耐药/复发的急性早幼粒细胞白血病

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-10 DOI: 10.1038/s41375-025-02738-9

Alessandra Zaza, Giuseppe Zardo, Cristina Banella, Sara Tucci, Elisabetta de Marinis, Martina Gentile, Serena Travaglini, Mariadomenica Divona, Tiziana Ottone, Germana Castelli, Anna Maria Cerio, Daniela F. Angelini, Isabella Faraoni, Raffaele Palmieri, Paquale Niscola, Emanuele Ammatuna, Adriano Venditti, Clara Nervi, Maria Teresa Voso, Gianfranco Catalano, Nelida Ines Noguera

{"title":"PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias","authors":"Alessandra Zaza, Giuseppe Zardo, Cristina Banella, Sara Tucci, Elisabetta de Marinis, Martina Gentile, Serena Travaglini, Mariadomenica Divona, Tiziana Ottone, Germana Castelli, Anna Maria Cerio, Daniela F. Angelini, Isabella Faraoni, Raffaele Palmieri, Paquale Niscola, Emanuele Ammatuna, Adriano Venditti, Clara Nervi, Maria Teresa Voso, Gianfranco Catalano, Nelida Ines Noguera","doi":"10.1038/s41375-025-02738-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02738-9","url":null,"abstract":"At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell’s growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse. We characterized the metabolic peculiarity and fuel requirement of PML::RARα expressing cells, to identify new targets for tailored therapies in resistant or relapsed APL patients. We analyzed cell metabolism in primary samples from seven APL patients, comparing them with normal CD34+ cells differentiated to promyelocyte and granulocyte, and different PML::RARα expressing cell lines. We show that the PML::RARα oncoprotein inhibits glycolysis, promotes tricarboxylic acid cycle (TCA), and favors long chain fatty acids (LCFA) catabolism. Targeting CD36 function, that promotes the cellular uptake of fatty acids to feed oxidative phosphorylation (OXPHOS), effectively restores sensitivity to ATO in NB4 ATO-resistant clones. Notably, our data demonstrate that glycolytic impairment via AKT inhibition by PML::RARα renders APL cells reliant on OXPHOS. This dependency confers high sensitivity to the VTX-AZA combination, suggesting the therapeutic efficacy of targeted combination treatment in resistant or relapsed APLs.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"24 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025303","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}

引用次数: 0

Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML 纵向单细胞分析揭示治疗耐药干细胞和肥大细胞与潜在的治疗儿科AML

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-10 DOI: 10.1038/s41375-025-02748-7

Denis Ohlstrom, Mojtaba Bakhtia, Hope Mumme, Marina Michaud, Alejandro De Janon Gutierrez, Deborah DeRyckere, Katherine E. Ferguson, Frank Chien, William Pilcher, Sarthak Satpathy, Sean Jordan, Douglas Graham, Swati Bhasin, Manoj Bhasin

{"title":"Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML","authors":"Denis Ohlstrom, Mojtaba Bakhtia, Hope Mumme, Marina Michaud, Alejandro De Janon Gutierrez, Deborah DeRyckere, Katherine E. Ferguson, Frank Chien, William Pilcher, Sarthak Satpathy, Sean Jordan, Douglas Graham, Swati Bhasin, Manoj Bhasin","doi":"10.1038/s41375-025-02748-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02748-7","url":null,"abstract":"Pediatric acute myeloid leukemia (pAML) is a heterogeneous malignancy driven by diverse cytogenetic mutations. While identification of cytogenetic lesions improved risk stratification, prognostication remains inadequate with 30% of standard-risk patients experiencing relapse within 5 years. To deeply characterize pAML heterogeneity and identify poor outcome-associated blast cell profiles, we performed an analysis on 708,285 cells from 164 bone marrow biopsies of 95 patients and 11 healthy controls. The longitudinal analysis on cell abundances at the time of disease diagnosis, end of induction, and relapse identified treatment resistant stem-like blast cells specific to RUNX1::RUNX1T1, FLT3-ITD, and CBFB::MYH11 patients that are associated with poor outcomes. Treatment resistant blast cells from RUNX1::RUNX1T1 were found to associate with T cell exhaustion, while those from FLT-ITD utilized enriched antioxidant metabolism to persist through treatment. Interestingly, the analysis also identified novel mast cell-like pAML associated with treatment resistance and poor outcomes. Deconvolution of ex vivo treatment data and subsequent in vitro validation identified bortezomib (RUNX1), ponatinib, and venetoclax (FLT3) as specifically potent against treatment resistant blasts from the respective cytogenetic groups. Our findings indicate immature and mature pAML subtypes are promising biomarkers for enhanced patient risk stratification and identifies targeted agents to increase their clearance after treatment.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"71 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025310","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}

引用次数: 0

Insights into germline predisposition to pediatric lymphoid malignancies 对儿童淋巴细胞恶性肿瘤的生殖系易感性的见解

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-09 DOI: 10.1038/s41375-025-02750-z

Roshina Thapa, Kim E. Nichols, Richa Sharma

引用次数: 0

Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model 依高龄及急性髓系白血病复合模型对venetoclax联合阿扎胞苷与阿扎胞苷单独治疗患者的结果进行分层

IF 11.4 1区医学

Leukemia Pub Date : 2025-09-05 DOI: 10.1038/s41375-025-02730-3

Adriano Venditti, Jing-Zhou Hou, Pierre Fenaux, Brian A. Jonas, Radovan Vrhovac, Pau Montesinos, Jacqueline S. Garcia, David Rizzieri, Michael J. Thirman, Meng Zhang, Jalaja Potluri, Catherine Miller, Mazaher Dhalla, Vinod Pullarkat

{"title":"Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model","authors":"Adriano Venditti, Jing-Zhou Hou, Pierre Fenaux, Brian A. Jonas, Radovan Vrhovac, Pau Montesinos, Jacqueline S. Garcia, David Rizzieri, Michael J. Thirman, Meng Zhang, Jalaja Potluri, Catherine Miller, Mazaher Dhalla, Vinod Pullarkat","doi":"10.1038/s41375-025-02730-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02730-3","url":null,"abstract":"Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs. placebo plus azacitidine in patients with newly diagnosed AML ineligible for IC from the phase 3 VIALE-A study (NCT02993523) and the phase 1b M14-358 study (NCT02203773), stratified by two methods to potentially assess frailty. The first method was age-based (75–79, 80–84, ≥85 years; n = 303 pooled from both studies) and the second was fitness-based using the AML composite model (AML-CM), a comorbidity-based model to estimate mortality risk (Group A, B, C; n = 380, from VIALE-A). Efficacy, including composite complete remission and overall survival, were improved with venetoclax plus azacitidine vs. placebo plus azacitidine across age and AML-CM groups. Safety was generally similar between age and AML-CM groups and no new safety signals were identified. Taken together, these data suggest that patients benefit from venetoclax plus azacitidine regardless of age or degree of frailty and the combination may be considered for patients with AML who may be deemed frail. Clinical trial information NCT02993523; NCT02203773.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"65 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995493","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}

引用次数: 0

Correction: Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial 修正：Olverembatinib联合venetoclax和低强度化疗治疗成人新诊断的费城染色体阳性急性淋巴细胞白血病：一项单中心，单臂，2期试验。

IF 13.4 1区医学

Leukemia Pub Date : 2025-09-05 DOI: 10.1038/s41375-025-02696-2

Xiaoyuan Gong, Wenbing Liu, Yuntao Liu, Qiuyun Fang, Runxia Gu, Kaiqi Liu, Dong Lin, Chunlin Zhou, Guangji Zhang, Benfa Gong, Shuning Wei, Yan Li, Shouyun Li, Ying Wang, Yimin Hu, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Hui Wei, Jianxiang Wang

引用次数: 0