Leukemia最新文献

{"title":"Prediction of resistance to hydroxyurea therapy in patients with polycythemia vera: a machine learning study (PV-AIM) validated in a prospective interventional phase IV trial (HU-F-AIM)","authors":"Florian H. Heidel, Valerio De Stefano, Matthias Zaiss, Jens Kisro, Eva Gückel, Susanne Großer, Mike W. Zuurman, Kirsi Manz, Kenneth Bryan, Armita Afsharinejad, Martin Griesshammer, Jean-Jacques Kiladjian","doi":"10.1038/s41375-025-02623-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02623-5","url":null,"abstract":"<p>Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thromboembolic (TE) risk and hematologic complications. Hydroxyurea (HU) serves as the most frequently used first-line cytoreductive therapy worldwide; however, resistance to HU (HU-RES) develops in a significant subset of patients, leading to increased morbidity and necessitating alternative treatments. This study, part of the PV-AIM project, employed machine learning techniques on real-world evidence (RWE) from the Optum® EHR database containing 82.960 PV patients to identify baseline predictors of HU-RES within the first 6–9 months of therapy. Using a Random Forest model, the study analyzed data from 1850 patients, focusing on laboratory parameters and clinical characteristics. Key predictive markers included red cell distribution width (RDW) and hemoglobin (HGB), showing the strongest association with HU-RES. A synergistic interaction between RDW and HGB was identified, enabling TE risk stratification. This study provides a robust framework for early detection of HU-RES using readily available clinical data, facilitating timely intervention. These findings underscore the importance of personalized treatment approaches in managing PV and highlight the utility of machine learning in enhancing predictive accuracy and clinical outcomes. Based on the results of PV-AIM we initiated an open-label, prospective, single-arm, interventional, phase IV study (HU-F-AIM) evaluating HU-resistance/intolerance. Validation of predictive biomarkers may facilitate identification of patients at risk of HU resistance who may benefit from alternative treatment options, possibly preventing ongoing phlebotomy during HU treatment, a frequent therapeutic choice in high-risk PV associated with early disease progression and increased thromboembolic complications. We propose an updated terminology that differentiates between true molecular resistance and clinical resistance, that may indicate the requirement for alternative therapeutic strategies.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872647","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":"Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time?","authors":"Nicolas Gazeau, David Beauvais, Rémi Tilmont, Micha Srour, Emmanuelle Ferrant, Violaine Safar, Ludovic Fouillet, Pascale Flandrin-Gresta, Nicolas Gower, Paul Chauvet, Nicolas Duployez, Benjamin Podvin, Julie Demaret, Sarah Huet, Pierre Sujobert, Hervé Ghesquières, Gandhi Damaj, Emmanuel Bachy, Franck Morschhauser, Ibrahim Yakoub-Agha, Maël Heiblig, Pierre Sesques","doi":"10.1038/s41375-025-02605-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02605-7","url":null,"abstract":"<p>Therapy-related myeloid neoplasms (t-MN), including myelodysplastic neoplasms (t-MDS) and acute myeloid leukemia (t-AML), have emerged as significant late complications after CAR T cell therapy. We retrospectively analyzed 539 patients with B cell lymphoma treated with CD19 directed CAR T cell therapy across four French centers. Cumulative incidences of t-MN was estimated with relapse or death treated as competing risk. Univariate and propensity score matching (PSM) analyses were conducted to assess risk factors with age and the number of prior treatments as covariates. After a median follow-up of 25 months, the cumulative incidence of t-MN was 4.5% at 2 years. T-MN occurred predominantly as t-MDS (62%) and t-AML (38%) with high cytogenetic risk. Median overall survival after t-MN diagnosis was 4.5 months. In univariate analysis, older age (<i>p </i>&lt; 0.01), higher MCV (<i>p </i>&lt; 0.01), and higher ICANS grade (<i>p </i>= 0.04) were associated with increased risk of t-MN. After PSM, MCV and ICANS grade remained significant risk factors. CAR T cell products with CD28 co-stimulatory domains trended towards higher t-MN risk (<i>p </i>= 0.09). NGS analysis showed that 85.7% of t-MN had pre-existing mutations, most commonly TP53. This study highlights t-MN as a severe late complication of CAR T cell therapy. MCV and ICANS grade were identified as key risk factors.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"2 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866630","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":"Possible impacts of cosmic radiation on leukemia development during human deep space exploration","authors":"Fay Ghani, Abba C. Zubair","doi":"10.1038/s41375-025-02624-4","DOIUrl":"https://doi.org/10.1038/s41375-025-02624-4","url":null,"abstract":"<p>With the advent of deep space exploration and ambitious plans to return humans to the Moon and journey onward to Mars, humans will face exposure to ionizing radiation beyond Earth’s atmosphere and magnetosphere. This is particularly concerning for the hematopoietic system that is sensitive to galactic cosmic rays (GCRs) during interplanetary missions. Epidemiological studies and animal studies implicate that exposure to ionizing radiation can cause leukemias, with recent consensus showing that almost all types of leukemias, even chronic lymphocytic leukemia, can be caused by ionizing radiation despite previous controversies. The possible deleterious effects of deep space travel on the formation, development, etiology, and pathophysiology of hematologic malignancies, specifically leukemias, remain largely unclear. The mechanism(s) by which ionizing radiations cause leukemia differs for different leukemia types and is poorly understood in the spaceflight environment, posing a serious health risk for future astronauts. This paper provides a comprehensive review of the various studies and evidence available on Earth and in space assessing the relationship between ionizing radiation and increased risk of leukemia. We also discuss the unique characteristics of leukemia in space, ethical considerations, risk assessments and potential challenges this may bring to astronauts and healthcare professionals as humanity continues to explore the cosmos.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"23 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866631","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":"ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker","authors":"Birna Thorvaldsdottir, Larry Mansouri, Lesley-Ann Sutton, Ferran Nadeu, Manja Meggendorfer, Helen Parker, Christian Brieghel, Stamatia Laidou, Riccardo Moia, Davide Rossi, Jana Kotaskova, Julio Delgado, Ana E. Rodríguez-Vicente, Rocío Benito, Gian Matteo Rigolin, Silvia Bonfiglio, Lydia Scarfò, Mattias Mattsson, Zadie Davis, Panagiotis Baliakas, Inmaculada Rapado, Fatima Miras, Joaquín Martinez-Lopez, Javier de la Serna, Jesús María Hernández Rivas, María José Larráyoz, María José Calasanz, Karin E. Smedby, Blanca Espinet, Anna Puiggros, Lars Bullinger, Francesc Bosch, Bárbara Tazón-Vega, Fanny Baran-Marszak, David Oscier, Florence Nguyen-Khac, Thorsten Zenz, Maria Jose Terol, Antonio Cuneo, María Hernández-Sánchez, Sarka Pospisilova, Gianluca Gaidano, Carsten U. Niemann, Elias Campo, Jonathan C. Strefford, Paolo Ghia, Kostas Stamatopoulos, Richard Rosenquist","doi":"10.1038/s41375-025-02615-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02615-5","url":null,"abstract":"<p>Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic <i>ATM</i> mutations remains uncertain. We evaluated the effects of <i>ATM</i> aberrations (del(11q) and/or <i>ATM</i> mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes. <i>ATM</i> mutations were present in 246 cases (6.8%), frequently co-occurring with del(11q) (112/246 cases, 45.5%). <i>ATM</i>-mutated patients displayed a different spectrum of genetic abnormalities when comparing IGHV-mutated (M-CLL) and unmutated (U-CLL) cases: M-CLL was enriched for <i>SF3B1</i> and <i>NFKBIE</i> mutations, whereas U-CLL showed mutual exclusivity with trisomy 12 and <i>TP53</i> mutations. Isolated <i>ATM</i> mutations were rare, affecting 1.2% of Binet A patients and &lt;1% of M-CLL cases. While univariable analysis revealed shorter TTFT for Binet A patients with any <i>ATM</i> aberration compared to <i>ATM</i>-wildtype, multivariable analysis identified only del(11q), trisomy 12, <i>SF3B1</i>, and <i>EGR2</i> mutations as independent prognosticators of shorter TTFT among Binet A patients and within M-CLL and U-CLL subgroups. These findings highlight del(11q), and not <i>ATM</i> mutations, as a key biomarker of increased risk of early progression and need for therapy, particularly in otherwise indolent M-CLL, providing insights into risk-stratification and therapeutic decision-making.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"45 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866632","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":"Age-related prognoses of genetic subtypes in B-cell acute lymphoblastic leukemia/lymphoma (B-ALL): insights from a decade of national data","authors":"Ting Zhou, Nicholas J. Short, Nitin Jain, Keyur P. Patel, Elias J. Jabbour, Hagop M. Kantarjian, L. Jeffrey Medeiros, J. Bryan Iorgulescu","doi":"10.1038/s41375-025-02588-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02588-5","url":null,"abstract":"<p>Recurrent chromosomal rearrangements and aneuploidies are founding genetic hallmarks in ~90% of B-lymphoblastic leukemia/lymphoma (B-ALL). Advances in our understanding of B-ALL genetics have transformed the modern classification and management of B-ALL, underscoring the integral role of molecular profiling [1,2,3,4]. Although contemporary risk-directed therapeutic regimens have improved outcomes for patients with B-ALL, not all ages benefit equally. Overall, patient survival rates are inversely correlated with age, from a 5-year overall survival (OS) of &gt;90% in children to &lt;30% in older adults (60+ yr) with standard chemotherapy-based management [5]. The etiology of this age-related decline in B-ALL survival rates remains unclear. Potential explanations include unique underlying distributions of genetic alterations (e.g., with adverse alterations such as <i>BCR</i>::<i>ABL1</i> enriched in older patients, whereas favorable genetic subtypes such as <i>ETV6</i>::<i>RUNX1</i> predominate in younger patients), and worse tolerance of chemotherapy in older adults [6, 7]. We therefore examined the relationships of B-ALL genetic subtype, patient age and outcomes; and whether rare B-ALL genetic subtypes exhibited unique clinicopathologic features.</p><p>Patients diagnosed with B-ALL between 2010 and 2021 were identified from the National Cancer Database (NCDB), which is maintained by the American College of Surgeons and American Cancer Society, and captures &gt;63% of new leukemia diagnoses across the United States from approximately 1,500 Commission on Cancer-accredited academic and community hospitals [8]. The NCDB contains deidentified national data that qualifies for human subjects research exemption. In 2010, cancer registries began collecting data for seven genetically defined B-ALL subtypes introduced in the World Health Organization (WHO) Classification 4th edition (and persist into the 5th edition), as defined by their ICD-O-3 codes: B-ALL with <i>BCR</i>::<i>ABL1</i> (9812/3), <i>ETV6</i>::<i>RUNX1</i> (9814/3), (high) hyperdiploidy (9815/3), <i>KMT2A</i>-rearrangement (9813/3), hypodiploidy (9816/3), <i>TCF3</i>::<i>PBX1</i> (9818/3), and <i>IGH</i>::<i>IL3</i> (9817/3) [1].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"260 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866621","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":"Time for a paradigm shift in immunotherapy-based BCMA/CD3 bispecific drug development in multiple myeloma","authors":"Xavier Leleu, Arthur Bobin, Andre Herbelin, Jean-Marc Gombert, S. Vincent Rajkumar","doi":"10.1038/s41375-025-02610-w","DOIUrl":"https://doi.org/10.1038/s41375-025-02610-w","url":null,"abstract":"<p>Drug development is deemed successful for patients not only on the basis of regulatory approval, but when the optimal, and ideally the minimal effective dose and schedule is determined [1]. This allows us to offer patients new approved treatments safely, and with the most optimized balance of risk and benefit. In clinical practice, many drugs in oncology are often given to patients at a dose and schedule that is considerably different from the one used in the pivotal trials to secure drug approval from regulators. These major changes in dose and schedule in clinical practice is usually the result of physicians encountering excess toxicity at approved doses, and reducing dose and dose intensity to improve tolerance and safety. In myeloma, for example, we use several drugs including bortezomib, carfilzomib, dexamethasone, thalidomide, pomalidomide at lower doses and or dose intensity than the doses used in initial pivotal trials. These post approval changes in dosing raises questions on the robustness and safety of the initial drug development processes used to secure approval of anticancer drugs which often carry high risks of toxicity compared to drugs used to treat other diseases.</p><p>Drug development in oncology has indeed evolved over the years from the concept of maximal tolerated dose (MTD) to a goal of determining the minimal effective dose (MED) to “minimize unnecessary drug exposure that will not lead to additional benefit to the patient but may increase the risk or severity of adverse events” [1]. However, with the advent of new immunotherapy options, we feel that MED may be difficult to establish and may not be a sufficient target. These new drugs are highly potent and may produce the best overall clinical benefit at doses and dosing intensity below MTD, and even what is initially perceived as the MED. As discussed below, longer-term results show that even the apparent MED may overestimate the required dose and dosing schedule leading to excess and unnecessary toxicity.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"7 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866623","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":"Ruxolitinib mediated paradoxical JAK2 hyperphosphorylation is due to the protection of activation loop tyrosines from phosphatases","authors":"Sivahari P. Gorantla, Lorenz Oelschläger, Gerin Prince, Jasmin Osius, Suresh Babu Kolluri, Yamil Maluje, Anke Fähnrich, Nancy Ernst, Alanis Barbosa Gulde, Ralf Joachim Ludwig, Timo Gemoll, Stephanie Fliedner, Wencke Walter, Torsten Haferlach, Niklas Gebauer, Hauke Busch, Justus Duyster, Nikolas von Bubnoff","doi":"10.1038/s41375-025-02594-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02594-7","url":null,"abstract":"<p>Myelofibrosis (MF) in 50% of cases is driven by an activating JAK2 mutation, mostly V617F. Ruxolinitib is approved for the treatment of MF. Responses to ruxolitinib in MF are of limited duration. Unexpectedly, treatment of JAK2-V617F expressing cells with ruxolitinib causes paradoxical hyperphosphorylation of JAK2 at activation loop Tyr1007/Tyr1008. The significance of ruxolitinib-induced JAK2 hyperphosphorylation is not well understood. We found that a ruxolitinib-resistant JAK2 variant (V617F + L983F) and a kinase dead mutant (JAK2-V617F + K882R) did not show paradoxical hyperphosphorylation after ruxolitinib treatment indicating that it is an intrinsic mechanism. Antibodies against pTyr1007/1008 failed to immunoprecipitate native JAK2-V617F in the presence of ruxolitinib, although JAK2-V617F was hyperphosphorylated at these sites, suggesting that in the presence of ruxolitinib the JAK2 activation loop is buried within the kinase domain. This stabilization of the activation loop conformation resulted in the protection of pTyr1007/1008 sites from phosphatases. Mutation of Arg975 and Lys999 to Ala reduced the phosphorylation at both Tyr1007/Tyr1008 residues, and notably, ruxolitinib treatment did not lead to JAK2 hyperphosphorylation. Importantly, hyperphosphorylated JAK2 after ruxolitinib dissociation displayed excess rebound activation of STAT5 target gene PIM kinase. Our results suggest a novel mode of kinase regulation by modulating kinase activity through conformational changes induced by ruxolitinib.</p><p>Subject categories: JAK2-V617F, Ruxolitinib, JAK2 hyperphosphorylation, Phosphatases action, PIM kinases</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"17 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862997","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":"MEK inhibitors are effective in Erdheim–Chester disease regardless of MAPK pathway mutations","authors":"Francesco Pegoraro, Fleur Cohen-Aubart, Matthias Papo, Francesco Catamerò, Jerome Razanamahery, Zahir Amoura, Jean-François Emile, Augusto Vaglio, Julien Haroche","doi":"10.1038/s41375-025-02614-6","DOIUrl":"https://doi.org/10.1038/s41375-025-02614-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"17 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866634","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":"National cancer system metrics and leukemia outcomes: an analysis of global data for pediatric and adult patients","authors":"James Fan Wu, Erin Jay G. Feliciano, Angelica Singh, Douglas Tremblay, Muhammad Bilal Abid, Edward Christopher Dee","doi":"10.1038/s41375-025-02598-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02598-3","url":null,"abstract":"<p>Globally, nearly 500,000 individuals were diagnosed with leukemia in 2022 alone [1]. In 2022, leukemia was among the top ten causes of cancer death in 71 countries in adults and the leading cause of cancer death in 96 countries in children [1, 2]. However, significant global heterogeneity exists in the incidence of various leukemias and their associated mortality [1, 3]. Less-resourced countries have been shown to have higher leukemia mortality-to-incidence ratios (MIR), highlighting health system inequities across countries [1]. For example, from 2010–2014, for pediatric acute lymphoblastic leukemia, the 5-year survival was 65.9% in Thailand versus 95.2% in Finland [3]. Survival disparities are mirrored among adults. From 2010–2014, for adult myeloid malignancies, the 5-year survival was 16.5% in Chile versus 57.5% in France [3].</p><p>While global disparities in both pediatric and adult leukemia have been documented [1, 3], further work is needed to elucidate how to translate these findings into cancer health system strengthening measures at the national and global levels. A detailed understanding of the levers that drive these cancer-specific infrastructures may inform health system planning specific to leukemia. Therefore, we used global health system data from the World Health Organization, the World Bank, the DIrectory of RAdiotherapy Centers, the United Nations Development Program, and the International Agency for Research on Cancer (IARC) to evaluate predictors of improved pediatric and adult leukemia outcomes globally.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"9 1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862996","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":"Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis","authors":"Mariusz Z. Ratajczak, Adrian Konopko, Justyna Jarczak, Michalina Kazek, Janina Ratajczak, Magdalena Kucia","doi":"10.1038/s41375-025-02613-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02613-7","url":null,"abstract":"<p>Hematopoietic cells and lymphocytes arise from a common stem cell for both lineages. This explains why similar signaling networks regulate the development and biological functions of these cells. One crucial regulatory mechanism involves interactions with soluble mediators of innate immunity, including activated elements of the complement cascade (ComC). For many years, ComC proteins were thought to be synthesized only in the liver and released into blood to be activated by one of the three proteolytic cascades. The regulatory effects of activated components of ComC on hematopoietic stem progenitor cells (HSPCs) and mature hematopoietic cells have been well demonstrated in the past. However, recent data indicate that complement proteins are also expressed in several cell types, including lymphocytes and innate immune cells. This intracellular complement network has been named the “complosome.” Recent evidence from our group shows that the complosome is also expressed in HSPCs and plays an important yet underappreciated role in the expansion, trafficking, and metabolism of these cells. We propose that the complosome, like its role in lymphocytes, is necessary for the optimal function of mitochondria in hematopoietic cells, including HSPCs. This opens a new area for investigation and potential pharmacological intervention into the complosome network in normal and malignant hematopoiesis.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"20 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862998","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}