Pub Date : 2025-12-15DOI: 10.1016/j.bneo.2025.100188
Steven Tessier , Jithma P. Abeykoon , Gordon Ruan , N. Nora Bennani , Mithun V. Shah , Karen L. Rech , Aishwarya Ravindran , Jay H. Ryu , Robert Vassallo , Matthew J. Koster , Caroline J. Davidge-Pitts , Lucinda M. Gruber , W. Oliver Tobin , Julio C. Sartori-Valinotti , Talal Hilal , Liuyan Jiang , Muhammad Alhaj Moustafa , Asra Z. Ahmed , Corrie R. Bach , Jason R. Young , Ronald S. Go
{"title":"Epidemiology of Erdheim-Chester disease in the United States: a SEER-based analysis","authors":"Steven Tessier , Jithma P. Abeykoon , Gordon Ruan , N. Nora Bennani , Mithun V. Shah , Karen L. Rech , Aishwarya Ravindran , Jay H. Ryu , Robert Vassallo , Matthew J. Koster , Caroline J. Davidge-Pitts , Lucinda M. Gruber , W. Oliver Tobin , Julio C. Sartori-Valinotti , Talal Hilal , Liuyan Jiang , Muhammad Alhaj Moustafa , Asra Z. Ahmed , Corrie R. Bach , Jason R. Young , Ronald S. Go","doi":"10.1016/j.bneo.2025.100188","DOIUrl":"10.1016/j.bneo.2025.100188","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977232","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}
Pub Date : 2025-11-25DOI: 10.1016/j.bneo.2025.100186
Nicholas Dunham ∗ , Zhenjia Wang ∗ , Yaseswini Neelamraju , Yan Guo , B. Bishal Paudel , Cem Meydan , Jorge A. Gandara , Fady A Abdelmalak , Hao Fan , Joyce Hardwick , Justin H. Layer , Tak Lee , Bernhard Maier , W. Hayes McDonald , Isaani Patnaik , Subhash Prajapati , Franck Rapaport , Caroline Sheridan , Gloria Sheynkman , Paul Zumbo , Francine E. Garrett-Bakelman †
Abstract
Relapsed acute myeloid leukemia (relAML) remains a clinical challenge. We have shown that epigenetic heterogeneity may contribute to transcriptional dysregulation and disease progression in AML, but the specific aberrant transcriptional programs have not been identified. We analyzed molecular profiles from patient-matched diagnostic and relapse AML specimens. A subset of differentially expressed genes (DEG) that were disparate in direction of expression change identified 2 patient subtypes. We predicted that transcriptional regulators (TR) might regulate the expression patterns observed. The expression patterns of the top TR predicted for the disparate genes associated with clinical outcomes. The top TR predicted for the disparate DEG and DEG identified in a patient-derived xenograft model of relAML included members of the LIM domain only 2 - LIM domain binding 1 - TAL BHLH TF1, erythroid differentiation factor (LMO2-LDB1-TAL1) multisubunit complex (LTMC). Analysis of DepMap data identified LMO2-dependent cells with a subset highly expressing TAL1, suggesting coordinated regulation. TAL1 copurified in immunoprecipitation for LMO2 and LDB1 followed by tandem mass spectrometry analysis in HEL and K562 cells, and results from chromatin immunoprecipitation experiments suggest significant co-occupancy of TAL1 and LDB1. Loss-of-function experiments targeting LMO2, LDB1, and TAL1 in AML cell lines associated with reduced cell growth, downregulation of cell cycle genes, and a negative association with gene expression patterns observed in relapsed patients with increased TAL1 expression. Our results from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LTMC in AML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for a subset of patients with AML.
{"title":"The LMO2-LDB1-TAL1 complex regulates transcription networks in acute myeloid leukemia","authors":"Nicholas Dunham ∗ , Zhenjia Wang ∗ , Yaseswini Neelamraju , Yan Guo , B. Bishal Paudel , Cem Meydan , Jorge A. Gandara , Fady A Abdelmalak , Hao Fan , Joyce Hardwick , Justin H. Layer , Tak Lee , Bernhard Maier , W. Hayes McDonald , Isaani Patnaik , Subhash Prajapati , Franck Rapaport , Caroline Sheridan , Gloria Sheynkman , Paul Zumbo , Francine E. Garrett-Bakelman †","doi":"10.1016/j.bneo.2025.100186","DOIUrl":"10.1016/j.bneo.2025.100186","url":null,"abstract":"<div><h3>Abstract</h3><div>Relapsed acute myeloid leukemia (relAML) remains a clinical challenge. We have shown that epigenetic heterogeneity may contribute to transcriptional dysregulation and disease progression in AML, but the specific aberrant transcriptional programs have not been identified. We analyzed molecular profiles from patient-matched diagnostic and relapse AML specimens. A subset of differentially expressed genes (DEG) that were disparate in direction of expression change identified 2 patient subtypes. We predicted that transcriptional regulators (TR) might regulate the expression patterns observed. The expression patterns of the top TR predicted for the disparate genes associated with clinical outcomes. The top TR predicted for the disparate DEG and DEG identified in a patient-derived xenograft model of relAML included members of the LIM domain only 2 - LIM domain binding 1 - TAL BHLH TF1, erythroid differentiation factor (LMO2-LDB1-TAL1) multisubunit complex (LTMC). Analysis of DepMap data identified LMO2-dependent cells with a subset highly expressing TAL1, suggesting coordinated regulation. TAL1 copurified in immunoprecipitation for LMO2 and LDB1 followed by tandem mass spectrometry analysis in HEL and K562 cells, and results from chromatin immunoprecipitation experiments suggest significant co-occupancy of TAL1 and LDB1. Loss-of-function experiments targeting LMO2, LDB1, and TAL1 in AML cell lines associated with reduced cell growth, downregulation of cell cycle genes, and a negative association with gene expression patterns observed in relapsed patients with increased TAL1 expression. Our results from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LTMC in AML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for a subset of patients with AML.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977231","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}
Pub Date : 2025-11-17DOI: 10.1016/j.bneo.2025.100185
Jonny Mendoza-Castrejon , Wei Yang , Elisabeth Denby , Rohini Muthukumar , Emily B. Casey , Riddhi M. Patel , Sarah K. Tasian , Jeffrey A. Magee
Abstract
Infant leukemias arise as B-cell acute lymphoblastic or acute myeloid leukemia. Most are driven by chromosomal rearrangements of the MLL/KMT2A gene (MLLr) and arise in utero, implying a fetal cell of origin. Fetal and neonatal hematopoietic progenitors have unique transcriptomes and epigenomes, raising the question of whether MLL fusion proteins activate distinct target genes during these early stages of life. In this study, we used a transgenic mouse model of MLL::ENL-driven leukemia to identify Skida1 as a target gene that is more highly induced in fetal and neonatal progenitors than in adult progenitors. SKIDA1 is highly expressed in human MLLr leukemias, and the encoded protein associates with the polycomb repressive complex 2. We show that Skida1 is dispensable for normal hematopoiesis, but it promotes B-cell priming and maintains MLL::ENL-expressing hematopoietic stem cells (HSCs) and multipotent progenitor cells during neonatal development. Conditional deletion of Skida1 has no effect on normal HSC function, yet it impairs B-cell production from neonatal MLL::ENL-expressing HSCs while leaving myeloid leukemogenesis unaffected. Temporally restricted targets of MLL fusion proteins, such as SKIDA1, can therefore tune cell fates at different ages, potentially influencing the types MLLr leukemias that arise at different ages.
{"title":"SKIDA1 sustains MLL::ENL-expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming","authors":"Jonny Mendoza-Castrejon , Wei Yang , Elisabeth Denby , Rohini Muthukumar , Emily B. Casey , Riddhi M. Patel , Sarah K. Tasian , Jeffrey A. Magee","doi":"10.1016/j.bneo.2025.100185","DOIUrl":"10.1016/j.bneo.2025.100185","url":null,"abstract":"<div><h3>Abstract</h3><div>Infant leukemias arise as B-cell acute lymphoblastic or acute myeloid leukemia. Most are driven by chromosomal rearrangements of the <em>MLL</em>/<em>KMT2A</em> gene (MLLr) and arise in utero, implying a fetal cell of origin. Fetal and neonatal hematopoietic progenitors have unique transcriptomes and epigenomes, raising the question of whether MLL fusion proteins activate distinct target genes during these early stages of life. In this study, we used a transgenic mouse model of MLL::ENL-driven leukemia to identify <em>Skida1</em> as a target gene that is more highly induced in fetal and neonatal progenitors than in adult progenitors. <em>SKIDA1</em> is highly expressed in human MLLr leukemias, and the encoded protein associates with the polycomb repressive complex 2. We show that <em>Skida1</em> is dispensable for normal hematopoiesis, but it promotes B-cell priming and maintains MLL::ENL-expressing hematopoietic stem cells (HSCs) and multipotent progenitor cells during neonatal development. Conditional deletion of <em>Skida1</em> has no effect on normal HSC function, yet it impairs B-cell production from neonatal MLL::ENL-expressing HSCs while leaving myeloid leukemogenesis unaffected. Temporally restricted targets of MLL fusion proteins, such as <em>SKIDA1</em>, can therefore tune cell fates at different ages, potentially influencing the types MLLr leukemias that arise at different ages.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884025","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}
Pub Date : 2025-11-06DOI: 10.1016/j.bneo.2025.100181
Andrew F. Berdel ∗ , Julian Ronnacker ∗ , Daniela V. Wenge , Lina J. Kolloch , Philipp Berning , Linus Angenendt , Tobias J. Brix , Annette Westermann , Klaus Wethmar , Torsten Kessler , Andrea Kerkhoff , Rolf M. Mesters , Christian Reicherts , Jan-Henrik Mikesch , Wolfgang E. Berdel , Georg Lenz , Christoph Schliemann , Matthias Stelljes
Abstract
The European LeukemiaNet (ELN) classification for acute myeloid leukemia (AML) incorporates cytogenetic and mutational risk profiles of AML to define separate risk groups that correlate with survival outcomes. Recommendations for postremission treatment (PRT) intensity, mainly allogeneic hematopoietic stem cell transplant, are based on these risk groups. In-depth genetically defined cohorts of registries or clinical trials, often reported as retrospective real-world validation cohorts, contain an inherent bias as patients were not treated according to recommendations matching time intervals of the respective ELN classification. We analyzed 662 patients with AML who received intensive induction therapy at our center between 2010 and 2022. Patients were classified according to ELN 2010 if treated between 2010 and 2016, and ELN 2017 if treated between 2017 and 2022. Overall survival (OS) and relapse-free survival (RFS) significantly improved for patients treated between 2017 and 2022 compared with those treated between 2010 and 2016 (4-year OS, 60% vs 40%; 4-year RFS, 54% vs 35%). To eliminate treatment bias, patients treated between 2017 and 2022 were retrospectively reclassified for genetic risk according to ELN 2010 and compared with regularly classified patients treated between 2010 and 2016. The improved outcome was particularly evident for intermediate-risk (IR) patients, whereas favorable and adverse subgroups showed no significant difference. This is, to our knowledge, the first analysis examining the impact of ELN-guided PRT in the context of treatment algorithms applied in the respective ELN time period. We conclude that the shift of risk groups between ELN 2010 and 2017, along with the resulting intensified PRT, contributed to significantly improved survival of patients with AML, particularly those with IR.
{"title":"Impact of European LeukemiaNet–guided postremission therapy on outcomes of patients with AML from 2010 to 2022","authors":"Andrew F. Berdel ∗ , Julian Ronnacker ∗ , Daniela V. Wenge , Lina J. Kolloch , Philipp Berning , Linus Angenendt , Tobias J. Brix , Annette Westermann , Klaus Wethmar , Torsten Kessler , Andrea Kerkhoff , Rolf M. Mesters , Christian Reicherts , Jan-Henrik Mikesch , Wolfgang E. Berdel , Georg Lenz , Christoph Schliemann , Matthias Stelljes","doi":"10.1016/j.bneo.2025.100181","DOIUrl":"10.1016/j.bneo.2025.100181","url":null,"abstract":"<div><h3>Abstract</h3><div>The European LeukemiaNet (ELN) classification for acute myeloid leukemia (AML) incorporates cytogenetic and mutational risk profiles of AML to define separate risk groups that correlate with survival outcomes. Recommendations for postremission treatment (PRT) intensity, mainly allogeneic hematopoietic stem cell transplant, are based on these risk groups. In-depth genetically defined cohorts of registries or clinical trials, often reported as retrospective real-world validation cohorts, contain an inherent bias as patients were not treated according to recommendations matching time intervals of the respective ELN classification. We analyzed 662 patients with AML who received intensive induction therapy at our center between 2010 and 2022. Patients were classified according to ELN 2010 if treated between 2010 and 2016, and ELN 2017 if treated between 2017 and 2022. Overall survival (OS) and relapse-free survival (RFS) significantly improved for patients treated between 2017 and 2022 compared with those treated between 2010 and 2016 (4-year OS, 60% vs 40%; 4-year RFS, 54% vs 35%). To eliminate treatment bias, patients treated between 2017 and 2022 were retrospectively reclassified for genetic risk according to ELN 2010 and compared with regularly classified patients treated between 2010 and 2016. The improved outcome was particularly evident for intermediate-risk (IR) patients, whereas favorable and adverse subgroups showed no significant difference. This is, to our knowledge, the first analysis examining the impact of ELN-guided PRT in the context of treatment algorithms applied in the respective ELN time period. We conclude that the shift of risk groups between ELN 2010 and 2017, along with the resulting intensified PRT, contributed to significantly improved survival of patients with AML, particularly those with IR.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791009","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}
Pub Date : 2025-11-06DOI: 10.1016/j.bneo.2025.100180
Hao-Yuan Wang , Fu-Chen Yang , Ching-Fen Yang , Chun-Kuang Tsai , Po-Chun Liu , Po-Shen Ko , Yao-Chung Liu , Jyh-Pyng Gau , Jin-Hwang Liu , Po-Min Chen , Nien-Jung Chen
Abstract
CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus–positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.
{"title":"Ratios of CD8 T lymphocytes to M-MDSCs (CD8MMR) predict prognosis in patients with untreated DLBCL","authors":"Hao-Yuan Wang , Fu-Chen Yang , Ching-Fen Yang , Chun-Kuang Tsai , Po-Chun Liu , Po-Shen Ko , Yao-Chung Liu , Jyh-Pyng Gau , Jin-Hwang Liu , Po-Min Chen , Nien-Jung Chen","doi":"10.1016/j.bneo.2025.100180","DOIUrl":"10.1016/j.bneo.2025.100180","url":null,"abstract":"<div><h3>Abstract</h3><div>CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus–positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840565","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}
Pub Date : 2025-11-06DOI: 10.1016/j.bneo.2025.100182
Alex C. H. Liu ∗ , Severine Cathelin ∗ , Dhanoop Manikoth Ayyathan ∗ , Yitong Yang , Farzaneh Aboualizadeh , Amina Abow , Gurbaksh Basi , Lance Li , David L. Dai , Abdula Maher , Eric Grignano , Mohsen Hosseini , Vivian Wang , Troy Ketela , Brandon Nicolay , Dylan M. Marchione , Adriana E. Tron , Andrea Arruda , Mark D. Minden , Steven M. Chan
Abstract
Clonal heterogeneity in acute myeloid leukemia (AML) can drive drug resistance because different clones may respond variably to treatments. Studying the evolution of these clones under the influence of therapeutic selective pressures is important for designing strategies to overcome drug resistance. Here, we used single-cell proteogenomic analysis to monitor the clonal evolution and differentiation of isocitrate dehydrogenase (IDH)–mutated AML in patient-derived xenografts (PDX) treated with IDH inhibitors alone or in combination with other antileukemic therapies. Furthermore, we generated mixed PDX models by coengrafting ≥2 leukemic samples into the same animal and used single-cell DNA sequencing to deconvolute their clonal composition. Using these models, we tracked clonal evolution under selective pressure from IDH inhibitors and combination therapies, identifying an association between WT1 mutations and ivosidenib (IDH1 inhibitor) monotherapy resistance, as well as an antagonism between ivosidenib and enasidenib (IDH2 inhibitor) when tested in IDH1-mutated cells. Our findings demonstrate how single-cell proteogenomic analysis of PDX models can illuminate drug resistance mechanisms and inform therapeutic strategies.
{"title":"Single-cell proteogenomic analysis of clonal evolution in PDX models of AML treated with IDH inhibitors","authors":"Alex C. H. Liu ∗ , Severine Cathelin ∗ , Dhanoop Manikoth Ayyathan ∗ , Yitong Yang , Farzaneh Aboualizadeh , Amina Abow , Gurbaksh Basi , Lance Li , David L. Dai , Abdula Maher , Eric Grignano , Mohsen Hosseini , Vivian Wang , Troy Ketela , Brandon Nicolay , Dylan M. Marchione , Adriana E. Tron , Andrea Arruda , Mark D. Minden , Steven M. Chan","doi":"10.1016/j.bneo.2025.100182","DOIUrl":"10.1016/j.bneo.2025.100182","url":null,"abstract":"<div><h3>Abstract</h3><div>Clonal heterogeneity in acute myeloid leukemia (AML) can drive drug resistance because different clones may respond variably to treatments. Studying the evolution of these clones under the influence of therapeutic selective pressures is important for designing strategies to overcome drug resistance. Here, we used single-cell proteogenomic analysis to monitor the clonal evolution and differentiation of isocitrate dehydrogenase (<em>IDH</em>)–mutated AML in patient-derived xenografts (PDX) treated with IDH inhibitors alone or in combination with other antileukemic therapies. Furthermore, we generated mixed PDX models by coengrafting ≥2 leukemic samples into the same animal and used single-cell DNA sequencing to deconvolute their clonal composition. Using these models, we tracked clonal evolution under selective pressure from IDH inhibitors and combination therapies, identifying an association between <em>WT1</em> mutations and ivosidenib (IDH1 inhibitor) monotherapy resistance, as well as an antagonism between ivosidenib and enasidenib (IDH2 inhibitor) when tested in <em>IDH1</em>-mutated cells. Our findings demonstrate how single-cell proteogenomic analysis of PDX models can illuminate drug resistance mechanisms and inform therapeutic strategies.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884026","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}
Pub Date : 2025-11-06DOI: 10.1016/j.bneo.2025.100183
Axel Sudria , Michael Loschi , Andrea Pinto , Laura Crousse , Sami Benachour , Rinzine Sammut , Frederic Chorin , Nicolas Mounier , Thomas Cluzeau
Abstract
Adapted physical activity (APA) has become an essential asset in the care of patients with cancer. Although its positive impact has mainly been studied regarding quality of life, few studies have focused on changes in lean mass (LM) and its determinants. This study reports the results of an APA program for inpatients in the hematology department of Nice University Hospital (France). Body composition analyses and physical tests were performed at admission and discharge. A total of 123 patients were analyzed with relative LM gain as the primary outcome. Over a median hospitalization duration of 33 days, the average observed LM variation was +0.32 kg (95% confidence interval [CI], 0.15-0.50), representing an average relative gain of +0.64% (95% CI, 0.28-1.01), with significant improvement in all physical tests. In multivariate analyses, a younger age and a shorter neutropenia duration were best predictive of LM gain. We show here that it is possible to maintain LM during hospitalization for hematology patients undergoing chemotherapy in a real-life setting.
{"title":"Adapted physical activity for hematology inpatients: focus on lean mass gain","authors":"Axel Sudria , Michael Loschi , Andrea Pinto , Laura Crousse , Sami Benachour , Rinzine Sammut , Frederic Chorin , Nicolas Mounier , Thomas Cluzeau","doi":"10.1016/j.bneo.2025.100183","DOIUrl":"10.1016/j.bneo.2025.100183","url":null,"abstract":"<div><h3>Abstract</h3><div>Adapted physical activity (APA) has become an essential asset in the care of patients with cancer. Although its positive impact has mainly been studied regarding quality of life, few studies have focused on changes in lean mass (LM) and its determinants. This study reports the results of an APA program for inpatients in the hematology department of Nice University Hospital (France). Body composition analyses and physical tests were performed at admission and discharge. A total of 123 patients were analyzed with relative LM gain as the primary outcome. Over a median hospitalization duration of 33 days, the average observed LM variation was +0.32 kg (95% confidence interval [CI], 0.15-0.50), representing an average relative gain of +0.64% (95% CI, 0.28-1.01), with significant improvement in all physical tests. In multivariate analyses, a younger age and a shorter neutropenia duration were best predictive of LM gain. We show here that it is possible to maintain LM during hospitalization for hematology patients undergoing chemotherapy in a real-life setting.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884027","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bneo.2025.100163
Ahmet Celal Toprak ∗ , Mutlu Mete ∗ , Julia J. Shi , Daria V. Babushok , Carmelo Gurnari , Jaroslaw P. Maciejewski , Zoe Bass , Zehra Tombul , Carlos. I. A. Santos , Munevver N. Duran , Hussein Awada , Ibrahim Ibrahim , Alper Olcal , Yusuf Ozcan , Leslie Guerrero , Julio Alvarenga Thiebaud , Taha Bat
Abstract
Patients with acquired aplastic anemia (AA) treated with immunosuppressive therapy (IST) face up to a 20% long-term risk of developing secondary myeloid neoplasms (sMNs), including acute myeloid leukemia and myelodysplastic syndromes. Although hematopoietic stem cell transplantation (HSCT) is curative and prevents sMNs, older patients and those lacking suitable donors have historically received IST as first-line therapy. Recent improvements in HSCT outcomes have expanded transplant eligibility, highlighting the need for tools to better identify patients at high risk for sMN. Validated predictive models could help guide early HSCT consideration or tailor surveillance strategies. We developed 2 binary machine learning models to predict sMN development in patients with acquired AA at clinically relevant time points: diagnosis (model 1) and 6 months after IST response (model 2). We analyzed data from 275 adult patients with AA treated at University of Texas Southwestern, Cleveland Clinic, and the Hospital of the University of Pennsylvania between 1975 and 2023. Seventy-nine clinical variables were collected, including demographics, somatic mutations, and treatment response. Neural networks were trained with leave-1-out crossvalidation. Both models achieved strong performance (area under the curve, 0.82; sensitivity, 0.82, specificity, 0.73). Shared key predictors included DNMT3A mutation, CUX1 mutation, total mutation count, and age. TET2 mutation was specific to model 1; paroxysmal nocturnal hemoglobinuria clone presence was unique to model 2. High-risk classification was significantly associated with worse overall survival (P < .0001). These findings support the feasibility of machine learning–based sMN risk prediction in AA. With training on larger data sets and external validation, these models may support individualized decision-making around HSCT and post-IST surveillance.
{"title":"Predicting secondary myeloid neoplasms in acquired aplastic anemia using machine learning models","authors":"Ahmet Celal Toprak ∗ , Mutlu Mete ∗ , Julia J. Shi , Daria V. Babushok , Carmelo Gurnari , Jaroslaw P. Maciejewski , Zoe Bass , Zehra Tombul , Carlos. I. A. Santos , Munevver N. Duran , Hussein Awada , Ibrahim Ibrahim , Alper Olcal , Yusuf Ozcan , Leslie Guerrero , Julio Alvarenga Thiebaud , Taha Bat","doi":"10.1016/j.bneo.2025.100163","DOIUrl":"10.1016/j.bneo.2025.100163","url":null,"abstract":"<div><h3>Abstract</h3><div>Patients with acquired aplastic anemia (AA) treated with immunosuppressive therapy (IST) face up to a 20% long-term risk of developing secondary myeloid neoplasms (sMNs), including acute myeloid leukemia and myelodysplastic syndromes. Although hematopoietic stem cell transplantation (HSCT) is curative and prevents sMNs, older patients and those lacking suitable donors have historically received IST as first-line therapy. Recent improvements in HSCT outcomes have expanded transplant eligibility, highlighting the need for tools to better identify patients at high risk for sMN. Validated predictive models could help guide early HSCT consideration or tailor surveillance strategies. We developed 2 binary machine learning models to predict sMN development in patients with acquired AA at clinically relevant time points: diagnosis (model 1) and 6 months after IST response (model 2). We analyzed data from 275 adult patients with AA treated at University of Texas Southwestern, Cleveland Clinic, and the Hospital of the University of Pennsylvania between 1975 and 2023. Seventy-nine clinical variables were collected, including demographics, somatic mutations, and treatment response. Neural networks were trained with leave-1-out crossvalidation. Both models achieved strong performance (area under the curve, 0.82; sensitivity, 0.82, specificity, 0.73). Shared key predictors included <em>DNMT3A</em> mutation, <em>CUX1</em> mutation, total mutation count, and age. <em>TET2</em> mutation was specific to model 1; paroxysmal nocturnal hemoglobinuria clone presence was unique to model 2. High-risk classification was significantly associated with worse overall survival (<em>P</em> < .0001). These findings support the feasibility of machine learning–based sMN risk prediction in AA. With training on larger data sets and external validation, these models may support individualized decision-making around HSCT and post-IST surveillance.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465198","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}
Pub Date : 2025-11-01DOI: 10.1016/j.bneo.2025.100169
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Pub Date : 2025-11-01DOI: 10.1016/j.bneo.2025.100159
Rong Wang ∗ , Jessica M. Stempel ∗ , Rory M. Shallis , Scott F. Huntington , Amer M. Zeidan , Natalia Neparidze , Mengyang Di , Jan Philipp Bewersdorf , Lourdes Mendez , Xiaomei Ma † , Nikolai A. Podoltsev †
Abstract
Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are classical Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) associated with an increased risk of development of second primary malignancies (SMs). The reasons for solid and lymphoid SMs are unclear, but a therapy-related effect has been invoked. Although an increased risk of nonmelanoma skin cancers is associated with the use of ruxolitinib (RUX), its influence on the development of other forms of SMs remains controversial. We conducted a retrospective cohort analysis to assess associations between RUX and SMs among older patients diagnosed with MPN from 2012 to 2019 in the Surveillance, Epidemiology, and End Results–Medicare–linked database. We identified 6043 patients (2396 with PV, 2944 with ET, 703 with MF) with a median age of 76 years (interquartile range [IQR], 71-82). After a median follow-up of 3.66 (IQR, 2.25-5.17) and 3.02 years (IQR, 1.84-4.75) for 513 RUX users and 5530 nonusers, respectively, 469 patients developed an SM: 383 solid and 86 lymphoid. In the multivariable proportional subdistribution hazard regression model with death as a competing risk, the risk of developing any SM did not differ by RUX use status (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.65-1.42; P = .84) or by proportion of days covered by RUX (every 10% increase; HR, 1.00; 95% CI, 0.96-1.05; P = .95). RUX exposure did not affect the risk of solid SM (HR, 0.77; 95% CI, 0.48-1.23; P = .27) or lymphoid SM (HR, 1.73; 95% CI, 0.79-3.80; P = .17). Our results suggest that RUX use does not increase the risk of SM in older patients with MPN.
真性红细胞增多症（PV）、原发性血小板增多症（ET）和骨髓纤维化（MF）是典型的费城染色体阴性骨髓增生性肿瘤（mpn），与发展为第二原发性恶性肿瘤（SMs）的风险增加有关。实性和淋巴样sm的原因尚不清楚，但与治疗相关的效应已被引用。虽然非黑色素瘤皮肤癌的风险增加与ruxolitinib （RUX）的使用有关，但其对其他形式的SMs发展的影响仍存在争议。我们在监测、流行病学和最终结果-医疗保险相关数据库中进行了回顾性队列分析，以评估2012年至2019年诊断为MPN的老年患者中RUX和SMs之间的关系。我们确定了6043例患者（2396例PV， 2944例ET， 703例MF），中位年龄为76岁（四分位数范围[IQR]， 71-82）。513名RUX使用者和5530名非使用者的中位随访时间分别为3.66年（IQR, 2.25-5.17）和3.02年（IQR, 1.84-4.75）， 469名患者发生SM: 383名实性SM和86名淋巴性SM。在以死亡为竞争风险的多变量比例亚分布风险回归模型中，发生任何SM的风险与RUX使用状况（风险比[HR]， 0.96； 95%置信区间[CI]， 0.65-1.42; P = 0.84）或RUX覆盖天数的比例（每增加10%；HR, 1.00; 95% CI, 0.96-1.05; P = 0.95）没有差异。暴露于RUX并不影响固体性SM（风险比，0.77;95% CI, 0.48-1.23; P = 0.27）或淋巴性SM（风险比，1.73;95% CI, 0.79-3.80; P = 0.17）的风险。我们的研究结果表明，RUX的使用不会增加老年MPN患者SM的风险。
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