LeukemiaPub Date : 2024-11-17DOI: 10.1038/s41375-024-02457-7
Ian M. Bouligny, Guillermo Montalban-Bravo, Koji Sasaki, Naval Daver, Elias Jabbour, Yesid Alvarado, Courtney D. DiNardo, Farhad Ravandi, Gautam Borthakur, Naveen Pemmaraju, Tapan Kadia, Lucia Masarova, Koichi Takahashi, Michael Andreeff, Alexandre Bazinet, Hui Yang, Rashmi Kanagal, Sherry Pierce, Meghan Meyer, Xuelin Huang, Guillermo Garcia-Manero
{"title":"A phase II trial of ipilimumab, nivolumab, or ipilimumab and nivolumab with or without azacitidine in relapsed or refractory myelodysplastic neoplasms","authors":"Ian M. Bouligny, Guillermo Montalban-Bravo, Koji Sasaki, Naval Daver, Elias Jabbour, Yesid Alvarado, Courtney D. DiNardo, Farhad Ravandi, Gautam Borthakur, Naveen Pemmaraju, Tapan Kadia, Lucia Masarova, Koichi Takahashi, Michael Andreeff, Alexandre Bazinet, Hui Yang, Rashmi Kanagal, Sherry Pierce, Meghan Meyer, Xuelin Huang, Guillermo Garcia-Manero","doi":"10.1038/s41375-024-02457-7","DOIUrl":"10.1038/s41375-024-02457-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"524-528"},"PeriodicalIF":12.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645944","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}
LeukemiaPub Date : 2024-11-17DOI: 10.1038/s41375-024-02454-w
Vignesh Krishnamoorthy, John Daly, Jimmy Kim, Lidia Piatnitca, Katie A. Yuen, Bhoj Kumar, Mehrnoush Taherzadeh Ghahfarrokhi, Tom Q. T. Bui, Parastoo Azadi, Ly P. Vu, Simon Wisnovsky
{"title":"The glycosyltransferase ST3GAL4 drives immune evasion in acute myeloid leukemia by synthesizing ligands for the glyco-immune checkpoint receptor Siglec-9","authors":"Vignesh Krishnamoorthy, John Daly, Jimmy Kim, Lidia Piatnitca, Katie A. Yuen, Bhoj Kumar, Mehrnoush Taherzadeh Ghahfarrokhi, Tom Q. T. Bui, Parastoo Azadi, Ly P. Vu, Simon Wisnovsky","doi":"10.1038/s41375-024-02454-w","DOIUrl":"10.1038/s41375-024-02454-w","url":null,"abstract":"Immunotherapy has demonstrated promise as a treatment for acute myeloid leukemia (AML). However, there is still an urgent need to identify new molecules that inhibit the immune response to AML. Most prior research in this area has focused on protein-protein interaction interfaces. While carbohydrates also regulate immune recognition, the role of cell-surface glycans in driving AML immune evasion is comparatively understudied. The Siglecs, for example, are an important family of inhibitory, glycan-binding signaling receptors that have emerged as prime targets for cancer immunotherapy in recent years. In this study, we find that AML cells express ligands for the receptor Siglec-9 at high levels. Integrated CRISPR genomic screening and clinical bioinformatic analysis identified ST3GAL4 as a potential driver of Siglec-9 ligand expression in AML. Depletion of ST3GAL4 by CRISPR-Cas9 knockout (KO) dramatically reduced the expression of Siglec-9 ligands in AML cells. Mass spectrometry analysis of cell-surface glycosylation in ST3GAL4 KO cells revealed that Siglec-9 primarily binds N-linked sialoglycans on these cell types. Finally, we found that ST3GAL4 KO enhanced the sensitivity of AML cells to phagocytosis by Siglec-9-expressing macrophages. This work reveals a novel axis of immune evasion and implicates ST3GAL4 as a possible target for immunotherapy in AML.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"346-359"},"PeriodicalIF":12.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02454-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645945","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}
LeukemiaPub Date : 2024-11-13DOI: 10.1038/s41375-024-02472-8
Qiangqiang Shao, Jedrzej Wykretowicz, Nan Hu, Karan Bedi, Mohamed Rizk, Isabella A. Malek, Surinder Kumar, David B. Lombard, Kerby Shedden, David Scott, Sami N. Malek
{"title":"Correction: Aberrant BCAT1 expression augments MTOR activity and accelerates disease progression in chronic lymphocytic leukemia","authors":"Qiangqiang Shao, Jedrzej Wykretowicz, Nan Hu, Karan Bedi, Mohamed Rizk, Isabella A. Malek, Surinder Kumar, David B. Lombard, Kerby Shedden, David Scott, Sami N. Malek","doi":"10.1038/s41375-024-02472-8","DOIUrl":"10.1038/s41375-024-02472-8","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"274-274"},"PeriodicalIF":12.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02472-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623310","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}
LeukemiaPub Date : 2024-11-13DOI: 10.1038/s41375-024-02464-8
Raúl Sánchez-Lanzas, Justin Barclay, Alexandros Hardas, Foteini Kalampalika, Amanda Jiménez-Pompa, Paolo Gallipoli, Miguel Ganuza
{"title":"A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones","authors":"Raúl Sánchez-Lanzas, Justin Barclay, Alexandros Hardas, Foteini Kalampalika, Amanda Jiménez-Pompa, Paolo Gallipoli, Miguel Ganuza","doi":"10.1038/s41375-024-02464-8","DOIUrl":"10.1038/s41375-024-02464-8","url":null,"abstract":"Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice. Provocatively, germline NOTCH3 ECD mutations perturbing cysteine numbers cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a type of vascular dementia, suggesting an unexpected link between CADASIL and CH. Here, we formally demonstrated that mouse hematopoietic stem and progenitor cells (HSPCs) expressing CADASIL-related NOTCH3C455R exhibit a proliferative advantage resulting in robust cellular expansion in vivo and in vitro. Co-expression of NOTCH3C455R and Dnmt3aR878H, homologous to a frequent human CH mutation, increased the fitness of NOTCH3C455R HSPCs, demonstrating their functional cooperation. Surprisingly, the presence of NOTCH3C455R hematopoietic cells supported the expansion of Dnmt3aR878H HSPCs in a non-cell autonomous fashion in vivo, strongly suggesting that CADASIL patients and asymptomatic carriers can be highly predisposed to DNMT3AR882H-driven CH. Considering that CADASIL-related NOTCH3 mutations are more frequent in the general population than anticipated (~1 carrier in 400 people), the effect of these NOTCH3 mutations on CH development should be considered.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"460-472"},"PeriodicalIF":12.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02464-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610340","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}
LeukemiaPub Date : 2024-11-12DOI: 10.1038/s41375-024-02466-6
Douglas Tremblay, Clifford Csizmar, Courtney D. DiNardo, Somedeb Ball, Noa Rippel, Danielle Hammond, Tapan M. Kadia, Farhad Ravandi, Kelly Chien, Grace Van Hyfte, Madhu Mazumdar, Antoine Saliba, Abhishek Mangaonkar, Terra Lasho, Aref Al-Kali, Marina Kremyanskaya, Jonathan Feld, Lewis R. Silverman, Rami Komrokji, John Mascarenhas, Eric Padron, Guillermo Garcia-Manero, David A. Sallman, Mrinal M. Patnaik, Guillermo Montalban-Bravo
{"title":"Venetoclax in combination with hypomethylating agents in chronic myelomonocytic leukemia: a propensity score matched multicenter cohort study","authors":"Douglas Tremblay, Clifford Csizmar, Courtney D. DiNardo, Somedeb Ball, Noa Rippel, Danielle Hammond, Tapan M. Kadia, Farhad Ravandi, Kelly Chien, Grace Van Hyfte, Madhu Mazumdar, Antoine Saliba, Abhishek Mangaonkar, Terra Lasho, Aref Al-Kali, Marina Kremyanskaya, Jonathan Feld, Lewis R. Silverman, Rami Komrokji, John Mascarenhas, Eric Padron, Guillermo Garcia-Manero, David A. Sallman, Mrinal M. Patnaik, Guillermo Montalban-Bravo","doi":"10.1038/s41375-024-02466-6","DOIUrl":"10.1038/s41375-024-02466-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"257-260"},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599700","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}
LeukemiaPub Date : 2024-11-11DOI: 10.1038/s41375-024-02453-x
I. L. Boueya, L. Sandhow, J. R. P. Albuquerque, R. Znaidi, D. Passaro
{"title":"Endothelial heterogeneity in bone marrow: insights across development, adult life and leukemia","authors":"I. L. Boueya, L. Sandhow, J. R. P. Albuquerque, R. Znaidi, D. Passaro","doi":"10.1038/s41375-024-02453-x","DOIUrl":"10.1038/s41375-024-02453-x","url":null,"abstract":"The central role of the endothelial microenvironment in orchestrating bone marrow (BM) homeostasis and hematopoietic support has been confirmed at various developmental stages and in adult life. The BM vasculature is crucial in mediating communication between BM parenchyma and circulating blood, displaying remarkable heterogeneity in structure and function. While vascular cell diversity in other tissues has long been recognized, the molecular basis of this phenomenon in BM is just now emerging. Over the past decade, single-cell approaches and microscopic observations have expanded our understanding of BM vasculature. While solely characterized for their paracrine properties in the past, recent advances have revolutionized our perception of endothelial function, revealing distinct anatomical locations associated with diverse endothelial cell states. The identification of phenotypic differences between normal and pathological conditions has therefore deepened our understanding of vascular dynamics and their impact on hematopoiesis in health and disease. In this review, we highlight key milestones and recent advances in understanding vascular heterogeneity within BM microenvironment during development, adulthood and aging. We also explore how leukemia affects this heterogeneity and how we can take this knowledge forward to improve clinical practices. By synthesizing existing literature, we aim to address unresolved questions and outline future research directions.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"8-24"},"PeriodicalIF":12.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02453-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597977","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}
LeukemiaPub Date : 2024-11-10DOI: 10.1038/s41375-024-02461-x
Shaohua Lei, Sujuan Jia, Sunitha Takalkar, Ti-Cheng Chang, Xiaotu Ma, Karol Szlachta, Ke Xu, Zhongshan Cheng, Yawei Hui, Selene C. Koo, Paul E. Mead, Qingsong Gao, Priyadarshini Kumar, Colin P. Bailey, Jobin Sunny, Alberto S. Pappo, Sara M. Federico, Giles W. Robinson, Amar Gajjar, Jeffrey E. Rubnitz, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Gang Wu, Jeffery M. Klco, Ruth G. Tatevossian, Charles G. Mullighan
{"title":"Genomic profiling of circulating tumor DNA for childhood cancers","authors":"Shaohua Lei, Sujuan Jia, Sunitha Takalkar, Ti-Cheng Chang, Xiaotu Ma, Karol Szlachta, Ke Xu, Zhongshan Cheng, Yawei Hui, Selene C. Koo, Paul E. Mead, Qingsong Gao, Priyadarshini Kumar, Colin P. Bailey, Jobin Sunny, Alberto S. Pappo, Sara M. Federico, Giles W. Robinson, Amar Gajjar, Jeffrey E. Rubnitz, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Gang Wu, Jeffery M. Klco, Ruth G. Tatevossian, Charles G. Mullighan","doi":"10.1038/s41375-024-02461-x","DOIUrl":"10.1038/s41375-024-02461-x","url":null,"abstract":"The utility of circulating tumor DNA (ctDNA) analysis has not been well-established for disease detection and monitoring of childhood cancers, especially leukemias. We developed PeCan-Seq, a deep sequencing method targeting diverse somatic genomic variants in cell-free samples in childhood cancer. Plasma samples were collected at diagnosis from 233 children with hematologic, solid and brain tumors. All children with hematologic malignancy (n = 177) had detectable ctDNA at diagnosis. The median ctDNA fraction was 0.77, and 97% of 789 expected tumor variants were identified, including sequence mutations, copy number variations, and structural variations responsible for oncogenic fusions. In contrast, ctDNA was detected in 19 of 38 solid tumor patients and 1 of 18 brain tumor patients. Somatic variants from ctDNA were correlated with minimal residual disease levels as determined by flow cytometry in serial plasma samples from patients with B-cell acute lymphoblastic leukemia (B-ALL). We showcase multi-tumor detection by ctDNA analysis for a patient with concurrent B-ALL and neuroblastoma. In conclusion, PeCan-seq sensitively identified heterogeneous ctDNA alterations from 1 mL plasma for childhood hematologic malignancies and a subset of solid tumors. PeCan-seq provides a robust, non-invasive approach to augment comprehensive genomic profiling at diagnosis and mutation-specific detection during disease monitoring.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"420-430"},"PeriodicalIF":12.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598088","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}
LeukemiaPub Date : 2024-11-08DOI: 10.1038/s41375-024-02459-5
Mali Salmon-Divon, Refael Meyuchas, Ofer Shpilberg, Elimelech Okon, Jamal Benhamida, Mariko Yabe, Kseniya Petrova-Drus, Tal Zvida-Bloch, May Basood, Roei Mazor, Benjamin H. Durham, Julien Haroche, Omar Abdel-Wahab, Eli L. Diamond, Oshrat Hershkovitz-Rokah
{"title":"The effect of methylation on the let-7-BCL2L1-BCL2 axis and the potential use of hypomethylating and BH3 mimetic drugs in histiocytic neoplasms","authors":"Mali Salmon-Divon, Refael Meyuchas, Ofer Shpilberg, Elimelech Okon, Jamal Benhamida, Mariko Yabe, Kseniya Petrova-Drus, Tal Zvida-Bloch, May Basood, Roei Mazor, Benjamin H. Durham, Julien Haroche, Omar Abdel-Wahab, Eli L. Diamond, Oshrat Hershkovitz-Rokah","doi":"10.1038/s41375-024-02459-5","DOIUrl":"10.1038/s41375-024-02459-5","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"516-519"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02459-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596944","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}
LeukemiaPub Date : 2024-11-08DOI: 10.1038/s41375-024-02397-2
Peng Li, F. N. U. Alnoor, Wei Xie, Margaret Williams, Julie Feusier, Yi Ding, Xiangrong Zhao, Gang Zheng, Chen Zhao, Arthur W. Zieske, Youli Zu, Philipp W. Raess, Srinivas Tantravahi, Afaf Osman, Ami B. Patel, Tsewang Tashi, Jay L. Patel, Anna P. Matynia, Madhu P. Menon, Rodney R. Miles, Jeffrey R. Jacobsen, Tracy I. George, Douglas W. Sborov, Philippe Szankasi, Paul Rindler, Devin Close, Robert S. Ohgami
{"title":"Rapid growth of acquired UBA1 mutations predisposes male patients to low-risk MDS","authors":"Peng Li, F. N. U. Alnoor, Wei Xie, Margaret Williams, Julie Feusier, Yi Ding, Xiangrong Zhao, Gang Zheng, Chen Zhao, Arthur W. Zieske, Youli Zu, Philipp W. Raess, Srinivas Tantravahi, Afaf Osman, Ami B. Patel, Tsewang Tashi, Jay L. Patel, Anna P. Matynia, Madhu P. Menon, Rodney R. Miles, Jeffrey R. Jacobsen, Tracy I. George, Douglas W. Sborov, Philippe Szankasi, Paul Rindler, Devin Close, Robert S. Ohgami","doi":"10.1038/s41375-024-02397-2","DOIUrl":"10.1038/s41375-024-02397-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"248-256"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596946","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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