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, Gebhard 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, Gebhard 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":"https://doi.org/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}
{"title":"Immune Escape of Acute Myeloid Leukemia after Transplantation.","authors":"Nguyen Huong Jenny Giang Ho, Nana Talvard-Balland, Natalie Köhler, Robert Zeiser","doi":"10.1158/2643-3230.BCD-24-0063","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-24-0063","url":null,"abstract":"<p><strong>Significance: </strong>We discuss the mechanisms of AML immune evasion including loss or downregulation of MHC class I and II, reduced TRAIL receptor expression, inhibitory metabolite production, inhibitory ligand expression, impaired proinflammatory cytokine production, and AML niche alterations.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF14"},"PeriodicalIF":11.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764910","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}
Fabio Luciani, Arman Safavi, Puneeth Guruprasad, Linhui Chen, Marco Ruella
{"title":"Advancing CAR T-cell Therapies with Artificial Intelligence: Opportunities and Challenges.","authors":"Fabio Luciani, Arman Safavi, Puneeth Guruprasad, Linhui Chen, Marco Ruella","doi":"10.1158/2643-3230.BCD-23-0240","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-23-0240","url":null,"abstract":"<p><p>Artificial intelligence could enhance chimeric antigen receptor T-cell therapy outcomes through optimization of all steps, from target identification, vector design, and manufacturing to personalized data-driven clinical decisions. In this report, we highlight steps toward unlocking this potential, including the need for standardized, comprehensive data repositories as a way for addressing barriers to artificial intelligence learning, such as data heterogeneity and patient privacy.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF4"},"PeriodicalIF":11.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731922","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":"Unleashing the Full Potential of Metabolic Interventions in T-ALL.","authors":"Victoria da Silva-Diz, Daniel Herranz","doi":"10.1158/2643-3230.BCD-25-0012","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-25-0012","url":null,"abstract":"<p><p>Drugs targeting metabolism have been effectively used in patients with T-cell acute lymphoblastic leukemia (T-ALL) for decades; still, the full therapeutic potential of targeting metabolism has not been completely exploited yet. Here, we highlight the critical need for metabolic biomarkers to advance precision medicine in T-ALL, explore the identification of novel metabolic vulnerabilities, and discuss the potential of targeted therapies and dietary interventions to optimize treatment outcomes.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF5"},"PeriodicalIF":11.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664582","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}
Ashwin R Iyer, Aishwarya Gurumurthy, Shih-Chun A Chu, Rohan Kodgule, Athalee R Aguilar, Travis Saari, Abdullah Ramzan, Jan Rosa, Juhi Gupta, Arvind Emmanuel, Cody N Hall, John S Runge, Anna B Owczarczyk, Jang W Cho, Matthew B Weiss, Rockwell Anyoha, Kristin Sikkink, Savanna Gemus, Charles P Fulco, Anamarija M Perry, Anthony D Schmitt, Jesse M Engreitz, Noah A Brown, Marcin P Cieslik, Russell J H Ryan
{"title":"Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.","authors":"Ashwin R Iyer, Aishwarya Gurumurthy, Shih-Chun A Chu, Rohan Kodgule, Athalee R Aguilar, Travis Saari, Abdullah Ramzan, Jan Rosa, Juhi Gupta, Arvind Emmanuel, Cody N Hall, John S Runge, Anna B Owczarczyk, Jang W Cho, Matthew B Weiss, Rockwell Anyoha, Kristin Sikkink, Savanna Gemus, Charles P Fulco, Anamarija M Perry, Anthony D Schmitt, Jesse M Engreitz, Noah A Brown, Marcin P Cieslik, Russell J H Ryan","doi":"10.1158/2643-3230.BCD-24-0126","DOIUrl":"10.1158/2643-3230.BCD-24-0126","url":null,"abstract":"<p><p>High expression of MYC and its target genes identify germinal center B-cell diffuse large B-cell lymphomas (GCB-DLBCL) associated with poor outcomes. We used CRISPR-interference profiling of human lymphoma cell lines to define essential enhancers in the MYC locus and non-immunoglobulin rearrangement partner loci, including a recurrent rearrangement between MYC and the BCL6 locus control region. GCB-DLBCL cell lines without MYC rearrangement are dependent on an evolutionarily-conserved enhancer we name \"germinal center MYC enhancer 1\" (GME-1), which is activated by the transcription factor complex of OCT2, OCA-B, and MEF2B, shows an active chromatin state in normal human and mouse germinal center B cells, and demonstrates selective acetylation and MYC promoter topological interactions in MYC-intact GCB-DLBCL biopsies. Whole-genome sequencing identified tandem copy gains of the GME-1 enhancer as a rare but recurrent event in DLBCL. Our findings shed new light on mechanisms that dysregulate MYC, a key driver of B cell malignancy.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606554","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}
{"title":"A model of intra-tumor and inter-patient heterogeneity explains clinical trials of curative combination therapy for lymphoma.","authors":"Amy E Pomeroy, Adam C Palmer","doi":"10.1158/2643-3230.BCD-24-0230","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-24-0230","url":null,"abstract":"<p><p>Models of tumor drug response have illuminated important concepts in oncology, but there remains a need for theory that combines intra-tumor and inter-patient heterogeneity to explain patient outcomes, especially for curative treatments. We present a mathematical model of multi-drug therapy that describes both cell-to-cell and patient-to-patient heterogeneity as distributions of drug sensitivity, and apply it to simulate curative combination therapies for Diffuse Large B-Cell Lymphoma (DLBCL). Simulated trials reproduced Progression-Free Survival and changes in circulating tumor DNA observed under standard therapy, and accurately predicted success or failure of nine randomized trials of first-line combinations based on drugs' efficacies in relapsed/refractory DLBCL. Finally, we used the model to explore how drug synergies, biomarkers, and subtype-specific endpoints could improve the chance of success of targeted combination therapies. This study offers a quantitative model of curative drug combinations and suggests that predictive simulations could aid the design of new regimens with curative intent.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493835","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}
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