Current Hematologic Malignancy Reports最新文献

{"title":"BRAF Alterations in Chronic Lymphocytic Leukemia: Genomic Landscape, Co-Mutation Patterns, and Clinical Relevance.","authors":"Abdulrahman Al-Abdulmalek, Eric Landry, Mohammed Abdulgayoom, Abdulrahman F Al-Mashdali, Ayman Abdullah Dalol, Bassam Muthanna, Jean-Pierre Routy, Shehab F Mohamed","doi":"10.1007/s11899-026-00780-7","DOIUrl":"https://doi.org/10.1007/s11899-026-00780-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>BRAF alterations are uncommon in chronic lymphocytic leukemia (CLL), yet increasing use of broad genomic profiling has identified them as a recurrent component of MAPK-pathway dysregulation. This revised review summarizes the reported frequency, mutation spectrum, co-mutation patterns, treatment-era associations, and clinical implications of BRAF alterations in adult CLL, with explicit separation of chemoimmunotherapy-dominant cohorts from targeted-therapy-era cohorts.</p><p><strong>Recent findings: </strong>Across published studies, BRAF mutations are usually detected in approximately 2-6% of unselected CLL cohorts, with higher frequencies in biologically enriched or treatment-selected populations. In chemoimmunotherapy-dominant cohorts, the clinically relevant signals are more often seen in treatment-timing endpoints such as time to first treatment, treatment-free survival, or time to next treatment than in overall survival alone. In targeted-therapy-era studies, including phase II and real-world cohorts, BRAF alterations recur as part of MAPK-pathway-driven clonal evolution at relapse after BTK-, PI3K-, or BCL2-directed therapy. Small pathology-based series also suggest that BRAF V600E is more frequent in Richter transformation than in untransformed CLL. By contrast, direct evidence for BRAF inhibitors in CLL is very limited, and available preclinical data do not support routine single-agent BRAF inhibition for the predominantly non-V600E lesions seen in CLL. Current evidence supports interpreting BRAF-mutated CLL within the broader RAS-RAF-MAPK-ERK signaling context rather than as a classical V600E-driven entity. At present, BRAF is best viewed as a biologic and resistance-relevant annotation rather than an established standalone prognostic biomarker or routine therapeutic target. Its clinical relevance appears greatest in trisomy 12-enriched disease, genomically complex cases, Richter transformation with V600E lesions, and treatment-exposed relapse where pathway-directed strategies may become increasingly important.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the BCR::ABL1 Kinase: Advances Beyond Imatinib in Chronic Myeloid Leukemia.","authors":"Zuhal Naderi, Teresa Sadras, Susan Branford, Naranie Shanmuganathan, Ilaria S Pagani","doi":"10.1007/s11899-026-00778-1","DOIUrl":"https://doi.org/10.1007/s11899-026-00778-1","url":null,"abstract":"","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline DDX41 Variants: Current Understanding and Future Directions.","authors":"Aldo A Acosta-Medina, Abhishek A Mangaonkar","doi":"10.1007/s11899-026-00779-0","DOIUrl":"https://doi.org/10.1007/s11899-026-00779-0","url":null,"abstract":"","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Signatures of Telomere Biology Disorders.","authors":"Luca Arcuri, Emma M Groarke, Sharon A Savage, Fernanda Gutierrez-Rodrigues","doi":"10.1007/s11899-026-00777-2","DOIUrl":"10.1007/s11899-026-00777-2","url":null,"abstract":"","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Pathogenesis and Targeted Therapies for Myeloproliferative Hypereosinophilic Neoplasms.","authors":"Colette Hanna, Joe Rizkallah, Nicole Charbel, Shereen Sakkal, Fadi G Haddad","doi":"10.1007/s11899-026-00775-4","DOIUrl":"10.1007/s11899-026-00775-4","url":null,"abstract":"","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intricate Dance Between Inflammation and Myeloproliferative Neoplasms: From Origins to Outcomes.","authors":"Angela G Fleischman","doi":"10.1007/s11899-026-00774-5","DOIUrl":"10.1007/s11899-026-00774-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Myeloproliferative neoplasms (MPNs) lie at the intersection of malignancy and chronic inflammatory disease. This review summarizes current understanding of how inflammation drives MPN pathogenesis, from clonal initiation to progression and symptom burden, and explores how emerging therapies modulate the inflammatory microenvironment.</p><p><strong>Recent findings: </strong>Evidence from human genetics, epidemiology, and experimental models shows that chronic inflammatory stress promotes the expansion of JAK2- and other MPN-associated clones. Inflammatory cytokine networks sustain myeloproliferation, reshape the bone marrow niche, and contribute to fibrosis. JAK inhibitors remain the cornerstone of therapy and exert much of their clinical benefit through suppression of cytokine signaling. Newer agents also mitigate inflammation through complementary mechanisms. Inflammation is inseparable from MPN biology and represents both a driver and a therapeutic target. Reframing MPN as a disorder of maladaptive immune and stromal interactions highlights opportunities to restore balance within this ecosystem and potentially alter disease course.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Targeted Therapy Falls Short: Unraveling Resistance Mechanisms in Chronic Lymphocytic Leukemia.","authors":"Samon Benrashid, Jennifer A Woyach","doi":"10.1007/s11899-026-00776-3","DOIUrl":"10.1007/s11899-026-00776-3","url":null,"abstract":"","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inotuzumab Ozogamicin in Clinical Practice: an Overview of Efficacy, Safety, and Real-World Applications.","authors":"Valerie Tran, Nandan Srinivasa, Caroline Tatum, Daniel Reed, Michael Keng","doi":"10.1007/s11899-026-00772-7","DOIUrl":"10.1007/s11899-026-00772-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute lymphoblastic leukemia (ALL) is a rare hematologic malignancy with a bimodal distribution of incidence in both pediatric/young adult and elderly patient populations. Despite the high complete remission rate, there is a high rate of relapse necessitating a need for therapy options in the relapsed/refractory setting. Given this, treatment paradigms for ALL have shifted towards targeted therapies and away from high-intensity chemotherapy. The efficacy of inotuzumab ozogamicin (InO) in the relapsed/refractory setting for pediatric and adult populations has led to incorporation of this targeted therapy into frontline regimens. In this review, the role of InO in the frontline, measurable residual disease (MRD) positive and relapsed/refractory settings is highlighted.</p><p><strong>Recent findings: </strong>InO is a directed antibody-drug conjugate that binds to CD22 on the surface of leukemic blasts. The cell internalizes InO, prompting enzymatic cleavage in the lysosome that releases calicheamicin, inducing double-strand DNA breaks and causing apoptosis. However, off-target effects can lead to severe adverse events such as hepatotoxicity, including veno-occlusive disease, and myelosuppression. Prior studies have supported its use in the relapsed or refractory treatment setting; however, newer studies incorporating InO in the frontline have shown promising results. Newer studies have also shown evidence of utilization of InO in specific sub-populations of B-cell ALL, including those with MRD-positive disease and Philadelphia-positive (Ph +) disease, and as bridging therapy with CAR T-cell therapy, and in the post-transplant maintenance setting. This review evaluated the effectiveness of InO in clinical practice, associated adverse events, future directions in specific patient populations. Despite recent advancements, patients with B-cell ALL tend to have poorer outcomes, especially in the adult population. Future research and larger scale prospective studies are indicated to evaluate the efficacy of InO in different lines of therapy.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Approaches for Measurable Residual Disease Assessment in Multiple Myeloma: Integrating NGS, Mass Spectrometry, and Next-Generation Flow Cytometry to Monitor Treatment Response.","authors":"Bhavesh Mohan Lal, Shaji K Kumar","doi":"10.1007/s11899-026-00771-8","DOIUrl":"https://doi.org/10.1007/s11899-026-00771-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Measurable residual disease (MRD) has emerged as the strongest prognostic biomarker in multiple myeloma (MM), providing a deeper assessment of treatment response than conventional serological tests. Sensitive MRD detection is helpful in risk stratification, prognostication, and early relapse prediction and is increasingly being used as an important clinical trial endpoint in MM. Moreover, MRD has emerged as a useful tool in guiding treatment intensity and duration.</p><p><strong>Recent findings: </strong>MRD can be assessed using bone marrow-based, peripheral blood-based, or imaging-based techniques. Bone marrow-based next-generation flow cytometry and next-generation sequencing, with a minimum sensitivity of 10^- 5, remain the current standard for MRD testing in MM. However, limitations like the need for frequent bone marrow aspirations and false negative results in patchy marrow involvement or isolated extramedullary disease have accelerated the interest in peripheral blood-based MRD tools. Mass spectrometry-based approaches, including intact protein mass spectrometry (MALDI-TOF assays like 'MASS-FIX' and 'EXENT') and clonotypic peptide mass spectrometry (such as 'EasyM' and 'M-Insight'), have evolved as highly sensitive peripheral blood-based MRD detection tools for relatively non-invasive dynamic MRD monitoring. Newer technologies like droplet digital PCR, circulating tumor cell analysis using enriched flow cytometry, cell-free DNA sequencing, and emerging epigenetic and fragmentomic profiling are in various phases of research and have the potential to revolutionize the way we monitor and treat MM. Finally, numerous active clinical trials worldwide are exploring the role of MRD in guiding treatment and are expected to shed light on the optimal approach to MRD assessments in routine clinical practice.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Impact of Non-driver Gene Mutations in Myelofibrosis.","authors":"Valentina Boldrini, Paola Guglielmelli, Alessandro M Vannucchi","doi":"10.1007/s11899-026-00773-6","DOIUrl":"10.1007/s11899-026-00773-6","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis and potential progression to a blast phase. This review provides a comprehensive overview of the current molecular landscape of MF beyond canonical driver mutations (JAK2, MPL or CALR), emphasizing insights gained from murine models that served as valuable tools for understanding disease mechanisms.</p><p><strong>Recent findings: </strong>High-throughput next-generation sequencing (NGS) has markedly enhanced our understanding of the molecular basis of MF, identifying numerous mutations beyond the canonical driver genes JAK2, MPL, and CALR, which are present in about 80% of patients. Additional mutations affect genes involved in DNA methylation (TET2, DNMT3A, IDH1, IDH2), histone modification (ASXL1, EZH2), mRNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), signaling pathways (CBL, NRAS, KRAS), and key transcription factors (RUNX1, NFE2, TP53). The presence and combination of these alterations influence clinical presentation, prognosis, and therapeutic response. This review offers an updated synthesis of the evolving molecular landscape of MF, highlighting how the intricate interplay among genetic alterations has deepened our understanding of disease heterogeneity, allowing refined risk stratification and therapeutic planning. Advances emerging from molecular research and experimental models are progressively translating into clinical practice, promoting more personalized and targeted approaches to the management of MF.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"21 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}