Miguel Quijada-Álamo, Grace Freed, Elvin Wagenblast
{"title":"Overcoming B-ALL Resistance to Targeted and Immune Therapies by Rational Combination Strategies.","authors":"Miguel Quijada-Álamo, Grace Freed, Elvin Wagenblast","doi":"10.1158/2643-3230.BCD-25-0036","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-25-0036","url":null,"abstract":"<p><p>Despite the remarkable efficacy of targeted therapies and immunotherapies in B-cell acute lymphoblastic leukemia (B-ALL), relapsed and refractory cases remain a major challenge. In this review, we discuss how integrating targeted agents with immunotherapy could help overcome resistance and improve long-term patient outcomes in B-ALL.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF5"},"PeriodicalIF":11.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Q&A: Louis Staudt on Molecular Classification of Cancer.","authors":"","doi":"10.1158/2643-3230.BCD-25-0133","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-25-0133","url":null,"abstract":"","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF4"},"PeriodicalIF":11.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Etienne Sollier, Anna Riedel, Umut H Toprak, Justyna A Wierzbinska, Dieter Weichenhan, Jan Philipp Schmid, Mariam Hakobyan, Aurore Touzart, Ekaterina Jahn, Binje Vick, Fiona Brown-Burke, Katherine Kelly, Simge Kelekci, Anastasija Pejkovska, Ashish Goyal, Marion Bähr, Kersten Breuer, Mei-Ju May Chen, Maria Llamazares-Prada, Mark Hartmann, Maximilian Schönung, Nadia Correia, Andreas Trumpp, Yomn Abdullah, Ursula Klingmüller, Sadaf S Mughal, Benedikt Brors, Frank Westermann, Elias Ulrich, Robert J Autry, Matthias Schlesner, Sebastian Vosberg, Tobias Herold, Philipp A Greif, Dietmar Pfeifer, Michael Lübbert, Thomas Fischer, Florian H Heidel, Claudia Gebhard, Wencke Walter, Torsten Haferlach, Ann-Kathrin Eisfeld, Krzysztof Mrózek, Deedra Nicolet, Lars Bullinger, Leonie Smeenk, Claudia Erpelinck-Verschueren, Roger Mulet-Lazaro, Ruud Delwel, Aurélie Ernst, Michael Scherer, Pavlo Lutsik, Irmela Jeremias, Konstanze Döhner, Hartmut Döhner, Daniel B Lipka, Christoph Plass
{"title":"Enhancer hijacking discovery in acute myeloid leukemia by pyjacker identifies MNX1 activation via deletion 7q.","authors":"Etienne Sollier, Anna Riedel, Umut H Toprak, Justyna A Wierzbinska, Dieter Weichenhan, Jan Philipp Schmid, Mariam Hakobyan, Aurore Touzart, Ekaterina Jahn, Binje Vick, Fiona Brown-Burke, Katherine Kelly, Simge Kelekci, Anastasija Pejkovska, Ashish Goyal, Marion Bähr, Kersten Breuer, Mei-Ju May Chen, Maria Llamazares-Prada, Mark Hartmann, Maximilian Schönung, Nadia Correia, Andreas Trumpp, Yomn Abdullah, Ursula Klingmüller, Sadaf S Mughal, Benedikt Brors, Frank Westermann, Elias Ulrich, Robert J Autry, Matthias Schlesner, Sebastian Vosberg, Tobias Herold, Philipp A Greif, Dietmar Pfeifer, Michael Lübbert, Thomas Fischer, Florian H Heidel, Claudia Gebhard, Wencke Walter, Torsten Haferlach, Ann-Kathrin Eisfeld, Krzysztof Mrózek, Deedra Nicolet, Lars Bullinger, Leonie Smeenk, Claudia Erpelinck-Verschueren, Roger Mulet-Lazaro, Ruud Delwel, Aurélie Ernst, Michael Scherer, Pavlo Lutsik, Irmela Jeremias, Konstanze Döhner, Hartmut Döhner, Daniel B Lipka, Christoph Plass","doi":"10.1158/2643-3230.BCD-24-0278","DOIUrl":"10.1158/2643-3230.BCD-24-0278","url":null,"abstract":"<p><p>Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. Genomic rearrangements that reposition active enhancers near proto-oncogenes, leading to their aberrant expression, have not been systematically investigated in AML. To facilitate the discovery of such \"enhancer hijacking\" events, we developed pyjacker, a computational tool, and applied it to 39 ckAML samples. Pyjacker identified several enhancer hijacking events in AML patient samples, including aberrant expression of motor neuron and pancreas homeobox 1 (MNX1), which can result from del(7)(q22q36) and is associated with hijacking of a CDK6 enhancer. MNX1 activation occurs in 1.4% of AML patients and shows significant co-occurrence with BCOR mutations. Through a xenograft mouse model, we demonstrated that MNX1 is required for leukemia cell fitness. Pyjacker is an easy-to-use, accurate, and broadly applicable tool for identifying consequences of genomic events driving tumorigenesis, especially when germline genomic data is missing.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher R Flowers, Rachel W Anantha, Veronica Leautaud, Pinkal Desai, Chancellor E Donald, Michelle A T Hildebrandt, Jean L Koff, Rulla M Tamimi, Wendy Cozen, Chijioke Nze, Ari M Melnick
{"title":"Addressing Health Disparities in Hematologic Malignancies: from Genes to Outreach.","authors":"Christopher R Flowers, Rachel W Anantha, Veronica Leautaud, Pinkal Desai, Chancellor E Donald, Michelle A T Hildebrandt, Jean L Koff, Rulla M Tamimi, Wendy Cozen, Chijioke Nze, Ari M Melnick","doi":"10.1158/2643-3230.BCD-24-0153","DOIUrl":"10.1158/2643-3230.BCD-24-0153","url":null,"abstract":"<p><strong>Significance: </strong>This review underscores our shared responsibility to champion multidimensional strategies rooted in basic and translational science, community involvement, and societal responsiveness for a meaningful impact. Unifying themes include the need to enhance collaborative infrastructure to engage laboratory researchers, epidemiologists, data scientists, clinicians, patients, community leaders, and policymakers; patient-level support services; outreach, education, and navigation for patients at the community level; recruitment and retention of underrepresented groups in the healthcare and research workforce; and funding for these efforts.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"79-93"},"PeriodicalIF":11.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher M Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P Papapetrou
{"title":"The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development.","authors":"Christopher M Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P Papapetrou","doi":"10.1158/2643-3230.BCD-24-0235","DOIUrl":"10.1158/2643-3230.BCD-24-0235","url":null,"abstract":"<p><strong>Significance: </strong>In recent years, remarkable technological advances have illuminated aspects of the pathogenesis of myeloid malignancies-yet outcomes for patients with these devastating diseases have not significantly improved. We posit that a synthesized view of the three dimensions through which hematopoietic cells transit during their healthy and diseased life-clonal evolution, stem cell hierarchy, and ontogeny-promises high yields in new insights into disease pathogenesis and new therapeutic avenues.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"94-109"},"PeriodicalIF":11.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval
{"title":"Dynamics of Immune Reconstitution and Impact on Outcomes across CAR-T Cell Products in Large B-cell Lymphoma.","authors":"Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval","doi":"10.1158/2643-3230.BCD-24-0163","DOIUrl":"10.1158/2643-3230.BCD-24-0163","url":null,"abstract":"<p><strong>Significance: </strong>This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival. These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"119-130"},"PeriodicalIF":11.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Konradin F Müskens, Nienke Wieringa, Maaike G J M van Bergen, Joëll E Bense, Brigit M Te Pas, Anne P J de Pagter, Arjan C Lankester, Marc B Bierings, Donna S Neuberg, Saskia Haitjema, Leontien C M Kremer, Gerwin A Huls, Stefan Nierkens, Joop H Jansen, Caroline A Lindemans, Aniek O de Graaf, Mirjam E Belderbos
{"title":"Increased Clonal Hematopoiesis in Long-term Survivors of Pediatric Hematopoietic Cell Transplantation.","authors":"Konradin F Müskens, Nienke Wieringa, Maaike G J M van Bergen, Joëll E Bense, Brigit M Te Pas, Anne P J de Pagter, Arjan C Lankester, Marc B Bierings, Donna S Neuberg, Saskia Haitjema, Leontien C M Kremer, Gerwin A Huls, Stefan Nierkens, Joop H Jansen, Caroline A Lindemans, Aniek O de Graaf, Mirjam E Belderbos","doi":"10.1158/2643-3230.BCD-24-0136","DOIUrl":"10.1158/2643-3230.BCD-24-0136","url":null,"abstract":"<p><strong>Significance: </strong>As survival of HCT recipients continues to improve, late treatment effects gain importance. We demonstrate that pediatric HCT recipients show increased risk of CH compared with age-matched controls. Prospective studies are crucial to understand the clinical implications of posttransplant CH in this young population.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"110-118"},"PeriodicalIF":11.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D DiNardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia
{"title":"Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia.","authors":"Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D DiNardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia","doi":"10.1158/2643-3230.BCD-24-0171","DOIUrl":"10.1158/2643-3230.BCD-24-0171","url":null,"abstract":"<p><strong>Significance: </strong>In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"23-37"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total (Immuno)Therapy: Version 2.0.","authors":"Susan Bal, Luciano J Costa","doi":"10.1158/2643-3230.BCD-24-0236","DOIUrl":"10.1158/2643-3230.BCD-24-0236","url":null,"abstract":"<p><p>Among patients with poly-refractory myeloma, autologous chimeric antigen receptor T-cell therapy offers exceptional promise. With the availability of bispecific antibodies, a total immunotherapeutic strategy in combination with chimeric antigen receptor T-cell therapy is now feasible. See related article by Fandrei et al., p. 38.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"10-12"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap.","authors":"Ola Landgren, Sean M Devlin","doi":"10.1158/2643-3230.BCD-24-0292","DOIUrl":"10.1158/2643-3230.BCD-24-0292","url":null,"abstract":"<p><strong>Significance: </strong>The acceptance of MRD-negative complete response as an endpoint that is reasonably likely to predict clinical benefit will allow for the design of streamlined clinical trials for accelerated approval, enabling significantly faster patient access to novel therapies. Cooperative efforts were required to obtain and analyze clinical trial data from multiple sponsors and to determine the best approach to analysis with a relatively limited number of available datasets. The process to evaluate MRD as an intermediate endpoint, undertaken jointly by myeloma researchers and industry, with feedback from the FDA, serves as a roadmap for other areas of oncology to develop intermediate endpoints.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"13-22"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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