Hematological Oncology最新文献

{"title":"DNA Replication Stress-Induced Transcriptome of Human Burkitt's Lymphoma Identifies Reciprocal Regulation Between MBD1 and BCL6 During Germinal Center-Derived B-Lymphomagenesis","authors":"Santosh Kumar Gothwal,&nbsp;Kyoko Oichai,&nbsp;Hongtae Kim,&nbsp;Kyungjae Myung,&nbsp;Jacqueline H. Barlow","doi":"10.1002/hon.70227","DOIUrl":"10.1002/hon.70227","url":null,"abstract":"<p>BCL6 is a master transcriptional regulator of germinal center (GC) B cells. <i>BCL6</i> is frequently translocated at the major translocation cluster (MTC) within intron 1 of the <i>BCL6</i> locus, a hotspot commonly rearranged in diffuse large B cell lymphomas (DLBCLs). <i>BCL6</i> amplifications are associated with therapeutic resistance and poor survival outcomes in hematological and solid cancers. However the mechanisms suppressing genome instability at the <i>BCL6</i>-MTC preventing <i>BCL6</i> rearragements remain unclear. Here, transcriptome analysis and genome-wide mapping of histone H3 lysine 4 trimethylation (H3K4me3) in hydroxyurea (HU)-treated Raji cells (a Burkitt's lymphoma model) revealed the induced expression of <i>MBD1,</i> encoding the DNA CpG methylation-binding protein. Functional studies using shRNA silencing and ectopic overexpression demonstrated that MBD1 suppresses <i>BCL6</i> transcription whose promoter harbors conserved CpG methylation sites, suggesting a DNA methylation-dependent regulation of <i>BCL6</i> trasncription by MBD1. Conversely, BCL6 repressed <i>MBD1</i> expression by binding to its promoter. <i>MBD1</i>-depleted Raji cells exhibited increased genomic instability at the <i>BCL6</i>-MTC upon HU treatment, heightened sensitivity to DNA replication inhibitors (HU, gemcitabine, and etoposide), and reduced tumorigenicity in xenograft mouse models. We propose that MBD1 prevents genomic instability at the <i>BCL6</i>-MTC to suppress DLBCL formation. Moreover, MBD1 promotes genomic stability and cell viability during DNA replication stress. MBD1 thus represents a potential therapeutic target for cancers exhibiting resistance to chemotherapies targeting DNA replication.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Heterogeneity of Diffuse Large B-Cell Lymphomas: A Comprehensive Genetic, Transcriptomic, and Phenotypic Profiling of B-Cell Lymphoma Cell Lines","authors":"Marina Pérez-Aguilera,&nbsp;Lucía Pedrosa,&nbsp;Sagrario Gómez,&nbsp;Sara Salazar-Ortego,&nbsp;Ismael Fernández-Miranda,&nbsp;Rafael Muñoz-Viana,&nbsp;Paloma Martín-Acosta,&nbsp;Beatriz L. Martín-Lunas,&nbsp;Rebeca Jimeno,&nbsp;Natalia Yanguas-Casás,&nbsp;Beatriz Horcajo,&nbsp;Giovana Roncador,&nbsp;José A. Martínez-Climent,&nbsp;Ana Ortega-Molina,&nbsp;Margarita Sánchez-Beato","doi":"10.1002/hon.70228","DOIUrl":"10.1002/hon.70228","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma, exhibiting significant molecular and clinical heterogeneity. Advances in classification integrating phenotypic, genetic, and transcriptomic features have improved diagnosis and prognosis. However, a comprehensive and integrated molecular characterization of DLBCL cell lines is still lacking, which limits their optimal use as reliable experimental models. We employed fluorescence in situ hybridization, immunohistochemistry, and targeted DNA and RNA sequencing to identify genetic subtypes and determine the cell of origin, providing a comprehensive characterization of 29 DLBCL cell lines through the integration of phenotypic, genomic, and transcriptomic data. Principal component analysis, gene set enrichment analysis (GSEA), differential expression profiling, and regulon analysis enabled us to dissect molecular heterogeneity. We achieved high concordance in genetic subtype assignment using multiple classification algorithms (2-S, LymphGen, and DLBclass). The DHIT/DZ signature and transcriptional profiling further revealed additional molecular complexity. Some DLBCL-NOS cases exhibited high-grade features, suggesting that gene expression signatures may capture biological aggressiveness better than cytogenetic methods. GSEA confirmed the relevance of signaling pathways across DLBCL subtypes, and regulatory network analysis identified specific transcription-factor activities that support these pathways. MCD cell lines showed increased NF-κB and STAT signaling, while EZB/MYC+ cell lines demonstrated increased proliferation and cell cycle regulation, along with decreased NF-κB/STAT activity. Our study offers a detailed molecular overview of DLBCL cell lines, underscoring their relevance for mechanistic and therapeutic research. The data highlights how integrating genetic and transcriptomic analyses can refine disease classification and guide personalized therapy strategies.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLT3-ITD Measurable Residual Disease in Acute Myeloid Leukemia: Recommended, but Not Yet Self-Sufficient","authors":"Francesco Albano","doi":"10.1002/hon.70236","DOIUrl":"10.1002/hon.70236","url":null,"abstract":"&lt;p&gt;The history of FMS-like tyrosine kinase 3-internal tandem duplication (&lt;i&gt;FLT3-ITD&lt;/i&gt;) in acute myeloid leukemia (AML) is that of a molecular marker that is biologically powerful, clinically influential, but methodologically irregular. &lt;i&gt;FLT3-ITD&lt;/i&gt; has been associated with an increased risk of relapse and adverse prognosis, becoming a central element in the molecular risk stratification of AML. The development of &lt;i&gt;FLT3&lt;/i&gt; inhibitors has further strengthened the clinical relevance of this marker, transforming &lt;i&gt;FLT3-ITD&lt;/i&gt; from a negative prognostic factor into a therapeutic target [&lt;span&gt;1&lt;/span&gt;]. Against this background, the use of &lt;i&gt;FLT3-ITD&lt;/i&gt; as a measurable residual disease (MRD) marker is conceptually attractive: a frequent, prognostically relevant, and pharmacologically targetable lesion could enable early identification of persistent disease and guide targeted therapeutic interventions. However, the trajectory of &lt;i&gt;FLT3-ITD&lt;/i&gt; as an MRD marker has been less straightforward than that of other molecular targets in AML, such as mutated &lt;i&gt;NPM1&lt;/i&gt; or fusion transcripts in core-binding factor leukemias [&lt;span&gt;2&lt;/span&gt;]. &lt;i&gt;FLT3-ITD&lt;/i&gt; is not a recurrent point mutation, but rather a heterogeneous family of insertional events that vary in number, mutational burden, length, insertion site, and sequence. This architecture has historically made the development of robust and generalizable MRD assays difficult. Beyond these technical constraints, substantial biological limitations must also be considered. &lt;i&gt;FLT3-ITD&lt;/i&gt; is often a signaling lesion acquired relatively late in the leukemic clonal hierarchy, frequently preceded by founder or preleukemic events [&lt;span&gt;3&lt;/span&gt;]. It may therefore be subclonal, multiclonal, unstable, acquired at relapse, or selectively suppressed by &lt;i&gt;FLT3&lt;/i&gt; inhibitor therapy [&lt;span&gt;4, 5&lt;/span&gt;]. In recent years, technical advances have reopened the possibility of using &lt;i&gt;FLT3-ITD&lt;/i&gt; as a target for MRD monitoring. Dedicated polymerase chain reaction–next-generation sequencing (PCR-NGS) approaches can longitudinally track ITD at very low burden by combining targeted amplification, deep sequencing, and dedicated bioinformatic pipelines [&lt;span&gt;6, 7&lt;/span&gt;]. Persistence of &lt;i&gt;FLT3-ITD&lt;/i&gt; detected by NGS-based methods during remission is associated with an increased risk of relapse and death, particularly in the pre-hematopoietic cell transplant (HCT) and peri-HCT settings [&lt;span&gt;8-13&lt;/span&gt;]. Moreover, recent data suggest that, in selected contexts, MRD results may help inform &lt;i&gt;FLT3&lt;/i&gt;-directed strategies, such as post-HCT maintenance with gilteritinib [&lt;span&gt;14&lt;/span&gt;]. This evolving evidence has been incorporated into recent ELN-DAVID recommendations, which now recognize a role for &lt;i&gt;FLT3-ITD&lt;/i&gt; ultra-high-sensitivity NGS MRD in selected clinical settings [&lt;span&gt;2, 15&lt;/span&gt;]. Nevertheless, the transition from measurability to full clinical actionability remains complex. The ability to detect ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Serum Free Light Chain Response in Newly Diagnosed Multiple Myeloma: Documented Earlier Than MRD and Complementary in Prognosis","authors":"Yubiao Pan,&nbsp;Yue Wang,&nbsp;Yaqin Xiong,&nbsp;Panpan Li,&nbsp;Chenqi Yu,&nbsp;Peng Liu","doi":"10.1002/hon.70234","DOIUrl":"10.1002/hon.70234","url":null,"abstract":"<p>Minimal residual disease (MRD) is the standard for deep response assessment in multiple myeloma but requires bone marrow sampling. Whether early serum free light chain (sFLC) response provides independent prognostic information in real-world, predominantly non-transplant patients remains unclear. We retrospectively analyzed 701 patients with newly diagnosed multiple myeloma treated at a single Chinese center (2015–2021). sFLC ratio normalization (IMWG range 0.26–1.65) during the first four induction cycles was assessed using a 4-month landmark to mitigate immortal time bias. Multivariable Cox models adjusted for R-ISS and age, with prespecified sensitivity analyses and direct comparison with established markers and MRD. Among 701 patients (median age 64 years; ASCT 12.6%), 433 (61.8%) were classified as FLC-normalized during C1-C4. FLC non-normalization was associated with inferior PFS (HR 2.10, 95% CI 1.60–2.76) and OS (HR 1.96, 95% CI 1.32–2.90) after adjustment for R-ISS stage and age. The association persisted in baseline-abnormal patients and after MRD adjustment. Adding sFLC status produced a modest improvement in model discrimination, supporting a complementary rather than stand-alone prognostic role. sFLC normalization was documented earlier than MRD negativity, a pattern that persisted in a paired-visit-restricted sensitivity analysis, although timing comparisons remain subject to retrospective assessment schedules. Early sFLC response was associated with outcomes in newly diagnosed multiple myeloma and provided complementary, incremental prognostic information beyond established risk factors and MRD. These findings support further prospective evaluation of sFLC normalization as a pragmatic blood-based marker for early risk stratification.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1 Trial of Duvelisib and Oral Azacitidine in Relapsed/Refractory T-Cell Lymphoma","authors":"Hayder Saeed,&nbsp;Melanie Mediavilla Varela,&nbsp;Eva Sahakian,&nbsp;Mahrukh Naqvi,&nbsp;Qianxing Mo,&nbsp;Ling Zhang,&nbsp;Rikesh Makanji,&nbsp;Yumeng Zhang,&nbsp;Ning Dong,&nbsp;Leidy Isenalumhe,&nbsp;Sameh Gaballa,&nbsp;Julio Chavez,&nbsp;Bijal Shah,&nbsp;Celeste Bello,&nbsp;Lubomir Sokol,&nbsp;Javier Pinilla-Ibarz","doi":"10.1002/hon.70235","DOIUrl":"10.1002/hon.70235","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Mature T-cell lymphomas (TCL) are aggressive malignancies with limited effective therapies. Duvelisib (DUV), a dual inhibitor of PI3K-δ and PI3K-γ, has shown promising activity in TCL. Azacitidine (AZA), a hypomethylating agent, has demonstrated efficacy in TCL and may enhance the activity of PI3K inhibitors through epigenetic modulation and immune regulation. We conducted a phase I, open-label, 3 + 3 dose-escalation study of oral duvelisib in combination with oral azacitidine (BMS-986345) in patients with relapsed or refractory TCL. The primary objective was to identify the maximum tolerated dose (MTD) of the combination. Fourteen patients (<i>N</i> = 14) were enrolled with a median age of 63.5 years. The median number of prior therapies was two. Grade ≥ 3 toxicities, expressed for the full treated population (<i>N</i> = 14), included neutropenia (29%), anemia (21%), AST elevation (21%), ALT elevation (14%), thrombocytopenia (14%), and leukocytosis (14%). Most adverse events were grade 1–2 and manageable. The ORR was 46% (<i>N</i> = 6), with 31% (<i>N</i> = 4) complete responses (CR) and 15% (<i>N</i> = 2) partial responses (PR). All four evaluable patients with a T-follicular-helper (TFH) phenotype achieved CR, a hypothesis-generating observation given the small denominator. Median PFS was 2.2 months (95% CI 1.8–NE) and median OS 10.2 months (95% CI 6.3–NE); however, median duration of response was not reached, and three responders were censored at the time of allogeneic transplant. On-treatment suppression of AKT phosphorylation was enhanced during combined therapy. Duvelisib plus oral azacitidine had a manageable safety profile and encouraging activity, particularly in the TFH subtype, where responses were deep and enabled a bridge to allogeneic transplant. Randomized evaluation focused on the TFH subtype is warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>NCT05065866</p>\u0000 </section>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Monocyte Subset Dynamics as Biomarker in Adult Histiocytosis: Association With Mutational Status, Kinase Inhibitor Exposure and Relapse Risk","authors":"Jerome Razanamahery,&nbsp;Caroline Raymond,&nbsp;Matthias Papo,&nbsp;Francesco Pegoraro,&nbsp;Julien Guy,&nbsp;Ludwig Serge Aho,&nbsp;Jean-François Emile,&nbsp;Maxime Samson,&nbsp;Sylvain Audia,&nbsp;Julien Haroche,&nbsp;Bernard Bonnotte","doi":"10.1002/hon.70233","DOIUrl":"https://doi.org/10.1002/hon.70233","url":null,"abstract":"&lt;p&gt;Histiocytoses are clonal disorders driven by pathological activation of the mitogen-activated protein kinase (MAPK) pathway (including &lt;i&gt;BRAF, MAP2K1, KRAS, NRAS&lt;/i&gt;) within CD68+ histiocytes [&lt;span&gt;1&lt;/span&gt;]. These conditions involve a complex interplay of clonal signals, immune responses, and inflammatory microenvironments. Clinical and radiological presentation are highly heterogenous depending on the histiocytosis type and mutational status. Despite significant therapeutic advances, relapses remain a challenge, particularly during treatment tapering or discontinuation [&lt;span&gt;2, 3&lt;/span&gt;]. Recent studies underscore the critical role of monocytes in histiocytosis [&lt;span&gt;4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Monocytes originate from hematopoietic stem cell progenitors and serve as essential precursors that infiltrate peripheral tissues to differentiate into macrophages (histiocytes) and dendritic cells [&lt;span&gt;6&lt;/span&gt;]. Human monocytes are characterized by three functionally distinct subsets (i.e., classical, intermediate and non-classical), each maintaining specific roles in both steady-state homeostasis and diseases [&lt;span&gt;7, 8&lt;/span&gt;]. Classical monocytes represent the primary myeloid-derived population and are implicated in the systemic inflammatory response and hematological cancer [&lt;span&gt;9&lt;/span&gt;]; notably, this subset is identified as the cellular vehicle for the &lt;i&gt;BRAF&lt;/i&gt;&lt;sup&gt;&lt;i&gt;V600E&lt;/i&gt;&lt;/sup&gt; mutation in “L-group” histiocytoses [&lt;span&gt;4, 5&lt;/span&gt;]. Conversely, non-classical monocytes are specialized for endothelial patrolling and vascular repair [&lt;span&gt;10&lt;/span&gt;], while the intermediate subset is characterized by a high capacity for antigen presentation alongside pro-inflammatory signaling [&lt;span&gt;11&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Research has revealed treatment-induced shifts in monocyte subset distribution [&lt;span&gt;12&lt;/span&gt;] and linked intermediate monocyte levels to disease control at single time points [&lt;span&gt;13&lt;/span&gt;]. For instance, &lt;i&gt;Papo and al&lt;/i&gt; [&lt;span&gt;12&lt;/span&gt;] reported a decrease in classical monocytes in patients treated for Erdheim-Chester Disease (ECD); while our recent work identified a decrease in intermediate monocytes in patients with controlled disease [&lt;span&gt;13&lt;/span&gt;]. However, comprehensive longitudinal analyses of monocyte subsets and their direct relationship to disease activity and relapse have not been explored in adult cohorts. To address this knowledge gap and to generate preliminary data on potential blood-based biomarkers, we conducted a pilot longitudinal analysis of monocyte subset dynamics, aiming to identify factors associated with their distribution and explore links to relapse status.&lt;/p&gt;&lt;p&gt;Our pilot study included 19 adult patients with histiocytosis: 8 Erdheim-Chester Disease (ECD) (4 with &lt;i&gt;BRAF&lt;/i&gt;&lt;sup&gt;&lt;i&gt;V600E&lt;/i&gt;&lt;/sup&gt; mutation), 6 Langerhans cell histiocytosis (LCH) (one with &lt;i&gt;BRAF&lt;/i&gt;&lt;sup&gt;&lt;i&gt;V600E&lt;/i&gt;&lt;/sup&gt; mutation, 2 with exon 12 deletion), one mixed LCH/ECD (&lt;i&gt;BRAF&lt;/i&gt;&lt;sup&gt;&lt;i&gt;V600E&lt;/i&gt;&lt;/sup&gt; mutation), and 4 Ro","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleoporin 98 Rearrangements in Acute Leukemia: A Genomic Landscape Study","authors":"Osama Batayneh,&nbsp;Natalie Danziger,&nbsp;Mahmoudreza Moein,&nbsp;Nour S. Naji,&nbsp;Dean Pavlick,&nbsp;Jeffrey S. Ross,&nbsp;Chelsea Marcus,&nbsp;Caleb Ho,&nbsp;Teresa Gentile,&nbsp;Zheng Zhou,&nbsp;Lincoln W. Pasquina","doi":"10.1002/hon.70231","DOIUrl":"10.1002/hon.70231","url":null,"abstract":"<p>Nucleoporin 98 rearrangements (<i>NUP98</i>re) occur in a wide range of hematologic malignancies including acute leukemias with a variety of fusion partners. <i>NUP98</i>re is associated with adverse prognosis, especially in children. We aimed to better understand the genomics of acute leukemias with <i>NUP98</i>re including fusion partners and co-occurring genomic alterations (GA). Results from 5905 patients with acute leukemia undergoing standard-of-care next generation sequencing on FoundationOneHeme were included for analysis. A total of 78 (1.3%) patient samples harbored <i>NUP98</i>re with a median age of 19 years compared with 62 years for the cases with no <i>NUP98</i> rearrangement (<i>NUP98</i>wt) (<i>p</i> &lt; 0.001). Patients with <i>NUP98</i>re were more frequently of admixed American ancestry (<i>p</i> &lt; 0.001). Among patients with acute myeloid leukemia, individual genomic alterations more frequently identified in <i>NUP98</i>re cases included <i>WT1</i> (77% vs. 11%, <i>p</i> &lt; 0.001) and FLT3 (49% vs. 26%, <i>p</i> &lt; 0.001); Alterations more frequent in the <i>NUP98</i>wt cohort included <i>NPM1</i>, <i>KMT2A</i>, <i>TET2, DNMT3A, ASXL1, SRSF2, STAG2,</i> and <i>BCOR</i> (all <i>p</i> &lt; 0.05). <i>NUP98</i>re are rare in patients with acute leukemia, more frequent in pediatrics and younger adults but distributed across all age groups. <i>NUP98</i>re is associated with a unique genomic landscape featuring increased frequencies of mutations with proliferative features (<i>FLT3</i> and <i>KRAS</i>) and growth suppression (<i>WT1</i>). Alterations in <i>WT1</i> had the highest co-occurrence rate in samples containing <i>NUP98</i>re. This work highlights the unique GA associated with <i>NUP98</i> and emphasizes the need for clinical studies to reveal underlying biologic mechanisms and enhance optimal management in the presence of potentially targetable alterations such as <i>NUP98</i>re.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matching-Adjusted Indirect Comparison of Gecacitinib, Fedratinib, Pacritinib, and Momelotinib in Second-Line Myelofibrosis Therapy","authors":"Yi Zhang,&nbsp;Hu Zhou,&nbsp;Qike Zhang,&nbsp;Qingchi Liu,&nbsp;Sujun Gao,&nbsp;Zhijian Xiao,&nbsp;Minghui Duan,&nbsp;Liangming Ma,&nbsp;Wei Wang,&nbsp;Huibing Dang,&nbsp;Guangsheng He,&nbsp;Hongmei Jing,&nbsp;Junmin Li,&nbsp;Haiping Yang,&nbsp;Huanling Zhu,&nbsp;Chunkang Chang,&nbsp;Yuqing Chen,&nbsp;Xin Du,&nbsp;Mei Hong,&nbsp;Xin Li,&nbsp;Jishi Wang,&nbsp;Na Xu,&nbsp;Shanshan Suo,&nbsp;Jie Jin","doi":"10.1002/hon.70230","DOIUrl":"10.1002/hon.70230","url":null,"abstract":"<div>\u0000 \u0000 <p>Ruxolitinib is first-line therapy for intermediate/high-risk myelofibrosis (MF), but ∼50% of patients discontinue within 1 year due to loss of efficacy or intolerance. Four JAK inhibitors (gecacitinib, fedratinib, pacritinib, momelotinib) are approved for ruxolitinib-pretreated MF, with no head-to-head trials comparing their efficacy and safety. This study used matching-adjusted indirect comparison (MAIC) to compare these four agents, aiming to provide evidence-based insights for treatment decision-making in ruxolitinib-resistant or intolerant MF. Individual patient data (IPD) of gecacitinib (100 mg BID; ZGJAK006/ZGJAK017, <i>n</i> = 78) and published data of comparators (fedratinib: JAKARTA-2/FREEDOM2; pacritinib: PAC203; momelotinib: SIMPLIFY-2/MOMENTUM) were analyzed. Eight baseline characteristics were matched. Efficacy outcomes (week-24 SVR35, TSS50, transfusion independence [TI]) were reported as odds ratios (ORs); safety as risk differences (RDs). Gecacitinib showed superior SVR35 versus fedratinib (JAKARTA-2: OR = 3.96, 95% CI = 1.37–11.39, <i>P</i> = 0.0108), pacritinib (PAC203: OR = 6.10, 95% CI = 1.54–24.23, <i>P</i> = 0.0101), and momelotinib (SIMPLIFY-2: OR = 8.65, 95% CI = 1.86–40.31, <i>P</i> = 0.0060), and superior TSS50 versus pacritinib (OR = 7.62 95% CI = 1.84–31.51, <i>P</i> = 0.0050) and momelotinib (MOMENTUM: OR = 7.52, 95% CI = 1.63–34.61, <i>P</i> = 0.0096). Numerically, gecacitinib had better TI. It also had significantly lower incidences of diarrhea, nausea, and AE-related treatment discontinuation. Hematologic AE profiles of gecacitinib varied by comparator cohort. Gecacitinib showed favorable efficacy and tolerability signals versus several comparators, suggesting it may be a valuable second-line option.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autologous Stem Cell Transplant Consolidation Is Associated With Improved Overall Survival in Angioimmunoblastic T-Cell Lymphoma: A Real-World National Cancer Database Study","authors":"Yu Tao,&nbsp;Huijun Li,&nbsp;Ayo S. Falade,&nbsp;Richard C. Godby,&nbsp;Steven R. Hwang,&nbsp;Grzegorz S. Nowakowski,&nbsp;Urshila Durani,&nbsp;Yun Kyoung Tiger,&nbsp;N. Nora Bennani,&nbsp;Stephen M. Ansell,&nbsp;Yucai Wang,&nbsp;Jihao Zhou","doi":"10.1002/hon.70222","DOIUrl":"10.1002/hon.70222","url":null,"abstract":"<div>\u0000 \u0000 <p>Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with poor outcomes, and the role of autologous stem cell transplantation (ASCT) as consolidation after frontline therapy remains controversial. We conducted a retrospective cohort study using the National Cancer Database, including adults diagnosed with AITL between 2004 and 2020 who received frontline systemic therapy. Patients were categorized as chemotherapy alone (Chemo) or chemotherapy followed by ASCT (Chemo + ASCT). To mitigate immortal time bias, prespecified landmark analyses were performed, with a 6-month landmark analysis as the primary approach and a 9-month landmark analysis as a sensitivity analysis. Multivariable Cox regression and propensity score weighting using inverse probability of treatment weighting for the average treatment effect were used to address measured confounding. Among 3996 patients receiving systemic therapy, 686 (17.2%) underwent ASCT. In the 6-month landmark analysis, ASCT was associated with improved overall survival (HR, 0.53; 95% CI, 0.45–0.62; <i>p</i> &lt; 0.001). Findings were consistent in the 9-month landmark analysis (HR, 0.58; 95% CI, 0.49–0.69; <i>p</i> &lt; 0.001) and IPTW-adjusted model (HR, 0.51; 95% CI, 0.44–0.60; <i>p</i> &lt; 0.001). In this large real-world cohort, ASCT consolidation was consistently associated with improved survival in patients with AITL. Although treatment-response data were unavailable and residual confounding cannot be excluded, these findings provide supportive real-world evidence and warrant prospective studies with treatment-timing and response data to better define patient selection.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Impact of BTK Inhibitor Exposure in LymphGen-Defined MCD Diffuse Large B-Cell Lymphoma","authors":"Shiyu Jiang,&nbsp;Yizhen Liu,&nbsp;Ran Wei,&nbsp;Wenhao Zhang,&nbsp;Longlong Bao,&nbsp;Jia Jin,&nbsp;Fangfang Lv,&nbsp;Chuanxu Liu,&nbsp;Xiaojian Liu,&nbsp;Hui Sun,&nbsp;Jiachen Wang,&nbsp;Rong Tao,&nbsp;Junning Cao,&nbsp;Xiaoyan Zhou,&nbsp;Qunling Zhang","doi":"10.1002/hon.70224","DOIUrl":"10.1002/hon.70224","url":null,"abstract":"<div>\u0000 \u0000 <p>The molecular subtype characterized by co-occurring MYD88 and CD79B alterations (MCD) represents a biologically distinct subset of diffuse large B-cell lymphoma (DLBCL) with chronic active B-cell receptor signaling and a high risk of central nervous system (CNS) involvement. The clinical impact of Bruton tyrosine kinase inhibitors (BTKi) in this subtype remains unclear. We retrospectively analyzed 155 patients with newly diagnosed DLBCL harboring genetic features consistent with the MCD subtype. At a median follow-up of 34.1 months, the estimated 3-year progression-free survival (PFS) rate was 76.1%. BTKi exposure (<i>n</i> = 56) was associated with significantly improved PFS compared with no BTKi exposure (3-year PFS: 93.8% vs. 66.6%, <i>p</i> &lt; 0.001) and remained independently associated with improved PFS after adjustment for IPI risk (HR 0.16, <i>p</i> &lt; 0.001). Overall survival did not differ significantly between groups. Notably, all 15 CNS relapse events occurred in patients who did not receive BTKi, whereas no CNS relapse was observed in the BTKi-treated group. BTKi exposure was independently associated with a markedly reduced risk of CNS relapse (HR 0.06, <i>p</i> = 0.002) after adjustment for CNS-IPI risk and CNS prophylaxis. These findings suggest that BTK inhibition may improve outcomes and mitigate CNS relapse in MCD DLBCL.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}