Annals of Hematology最新文献

{"title":"Epstein-barr virus-associated hemophagocytic lymphohistiocytosis after antithymocyte globulin-conditioned allogeneic hematopoietic stem cell transplantation: a single-center case series","authors":"Ingerid Weum Abrahamsen, Anders Eivind Myhre, Camilla Dao Vo, Tobias Gedde-Dahl, Tor Henrik Tvedt","doi":"10.1007/s00277-026-07307-3","DOIUrl":"10.1007/s00277-026-07307-3","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07307-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189621","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":"Primary thyroid diffuse large B-cell lymphoma: a case report and focused review of the literature","authors":"Kürsat Kirkgöz,&nbsp;Katja Weisel,&nbsp;Carsten Bokemeyer,&nbsp;Susanne von Kroge","doi":"10.1007/s00277-026-07303-7","DOIUrl":"10.1007/s00277-026-07303-7","url":null,"abstract":"<div><p>Primary thyroid diffuse large B-cell lymphoma (DLBCL) is a rare subset of primary extranodal DLBCL. Thus, there are limited evidence-based specific recommendations regarding its diagnosis and treatment. We present a case report of a patient with relapsed primary thyroid DLBCL, followed by a focused literature review covering key epidemiological, diagnostic, and therapeutic aspects. In 2017, a 74-year-old woman was diagnosed with primary thyroid non-GCB-type DLBCL (Ann Arbor IE, IPI 2) after presenting with dyspnoea, hoarseness, and cough. Treatment with R-CHOP and CNS prophylaxis achieved complete remission. Six years later, an isolated relapse occurred in the contralateral thyroid gland. The patient was treated with Pola-R-miniCHP (off-label), resulting in complete remission again. In the focused literature review core needle or surgical biopsy was found to be important for reliable histopathological characterization, while first-line treatment mainly consisted of rituximab-containing chemoimmunotherapy, occasionally combined with radiotherapy. Surgery was largely limited to diagnostic purposes. Reported 5-year overall survival rates ranged from 57% to 88%, whereas relapse or refractory disease and central nervous system involvement were rare. Registry-based studies, especially those focusing on primary extranodal DLBCL, are necessary to develop evidence-based treatment guidelines for these patients.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07303-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132997","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":"Final results of the CARO study: real-world adherence, effectiveness and patient-reported quality of life with carfilzomib-based regimens in German patients with relapsed/refractory multiple myeloma","authors":"Karin Potthoff,&nbsp;Jens Uhlig,&nbsp;Eyck von der Heyde,&nbsp;Christoph Losem,&nbsp;Arnd Nusch,&nbsp;Andreas Ammon,&nbsp;Björn Schöttker,&nbsp;Holger Schulz,&nbsp;Jan Janssen,&nbsp;Manfred Welslau,&nbsp;Stefan Wilop,&nbsp;Corinne Vannier,&nbsp;Johanna Hanselmann,&nbsp;Laura Serrer,&nbsp;Sandra M. Woerner,&nbsp;Sophie Koszinowski,&nbsp;Monika Engelhardt,&nbsp;Wolfgang Knauf","doi":"10.1007/s00277-026-07302-8","DOIUrl":"10.1007/s00277-026-07302-8","url":null,"abstract":"<div><p>The prospective, multicenter, non-interventional study CARO (NCT02970747) investigated adherence, effectiveness, quality of life and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in German routine clinical practice. CARO included 359 patients at 69 sites and evaluated three carfilzomib-based treatment regimens: Carfilzomib with lenalidomide and dexamethasone (KRd), with dexamethasone only (Kd) or with daratumumab and dexamethasone (KdD). Across cohorts, patients’ adherence to carfilzomib was &gt; 90%, while effectiveness was in line with previous data from both randomized clinical trials and real-world studies. Median PFS (95% CI) was 17.5 months (14.5, 24.7 [KRd]), 13.4 months (7.3, 18.1 [Kd]) and 20.1 months (10.9, 26.6 [KdD]), respectively. Median OS was 38.9 months (31.5, 51.4 [KRd]), 24.6 months (17.8, 36.8 [Kd]) and not reached (21.9, NA [KdD]). Patients’ quality of life remained stable during treatment, while pain parameters improved after 6 months of treatment. CARO provides real-world evidence that KRd, Kd, and KdD combinations achieve clinically meaningful outcomes in everyday practice and demonstrates patients’ excellent treatment adherence.</p><p>ClinicalTrials.gov identifier: NCT02970747</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07302-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132643","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 SPIZ study: rationale and protocol of a randomized controlled trial to optimize interdisciplinary care of patients following cellular therapy through a digitally supported, cross-regional and cross-sectoral care model","authors":"Martin M. K. Schneider,&nbsp;Gabriele Müller,&nbsp;Sabrina Herbst,&nbsp;Julia Slesaczeck,&nbsp;Roman Schmädig,&nbsp;Franziska Schmidt,&nbsp;Thomas Illmer,&nbsp;Lynn Leppla,&nbsp;Sabine Valenta,&nbsp;Sabina De Geest,&nbsp;Alexandra Teynor,&nbsp;Markus Wolfien,&nbsp;Alice Ernst,&nbsp;Lara Bischof,&nbsp;Jochen Schmitt,&nbsp;Mathias Hänel,&nbsp;Klaus H. Metzeler,&nbsp;Uwe Platzbecker,&nbsp;Vladan Vučinić,&nbsp;Johannes Schetelig,&nbsp;Martin Bornhäuser,&nbsp;Jan Moritz Middeke,&nbsp;Katharina Egger-Heidrich","doi":"10.1007/s00277-026-07290-9","DOIUrl":"10.1007/s00277-026-07290-9","url":null,"abstract":"<div><p>Allogeneic hematopoietic cell transplantation (alloHCT) and chimeric antigen receptor T (CAR T)-cell therapy represent established therapeutic modalities for selected hematologic malignancies but are associated with substantial morbidity, high healthcare costs, and a considerable risk of severe complications, including death. This necessitates specialized and continuous post-treatment care, which is currently insufficiently standardized and still largely delivered predominantly through in-person and nonintegrated processes. We aimed to develop a comprehensive and innovative post-treatment care program for patients after alloHCT and CAR T-cell therapy based on an interdisciplinary, digitally supported, cross-regional and, cross-sectoral approach, and to evaluate its effectiveness in a randomized controlled trial (RCT). Developed by a multidisciplinary team, the intervention involves case managers and home visits by onco nurses, supported by digital components. These include patient-reported monitoring of vital signs and symptoms via a mobile application, video consultations, and virtual case conferences with community-based hematologists. The evaluation of effectiveness includes both quantitative outcomes, such as mortality and rehospitalization rates, and qualitative data derived from semi-structured interviews. The required ethics approvals were obtained in due time, and the three study centers were successfully initiated in 2024. As of January 2026, recruitment has been completed, and a total of 306 patients were successfully enrolled and randomized in a 1:1 ratio to receive either the SPIZ intervention or routine care. Funded and supported by the Federal Joint Committee (G-BA), a positive evaluation could facilitate the integration of the proposed care model into routine clinical practice, thereby strengthening post-treatment care for patients undergoing cellular therapy across Germany.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07290-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035244","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":"Obstetric and thrombotic outcomes among pregnant patients with myeloproliferative neoplasms: a propensity score matched real-world analysis","authors":"Nikhil Vojjala,&nbsp;Sambasiva Rao Srungavarapu,&nbsp;Sushmitha Nanjareddy,&nbsp;Mani Vignesh Kannan,&nbsp;Rishab Prabhu,&nbsp;Camelia Arsene,&nbsp;Geetha Krishnamoorthy,&nbsp;Vijendra Singh","doi":"10.1007/s00277-026-07285-6","DOIUrl":"10.1007/s00277-026-07285-6","url":null,"abstract":"<div><p>Pregnancies complicated by BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are associated with increased maternal and thrombotic risk; however, large real-world comparative data remain limited. We performed a multicenter retrospective propensity score-matched cohort study using the TriNetX database to evaluate maternal, obstetric, and thrombotic outcomes among pregnant patients with MPN compared with matched non-MPN controls. Baseline demographics, comorbidities, and antithrombotic medication use were balanced after matching (standardized mean difference &lt; 0.1). Among 4,467,127 pregnancies, 4,563 patients had MPN, most commonly essential thrombocytosis (85%). Compared with matched controls, MPN pregnancies had significantly higher all-cause mortality (1.1% vs. 0.2%; hazard ratio [HR] 5.4, 95% CI 2.7–10.8), gestational hypertension (11.1% vs. 7.8%; HR 1.3, 95% CI 1.1–1.5), preeclampsia/eclampsia (10.4% vs. 5.3%; HR 1.8, 95% CI 1.6–2.1), preterm labor (6.1% vs. 3.7%; HR 1.5, 95% CI 1.2–1.8), intrauterine growth restriction (7.3% vs. 5.1%; HR 1.3, 95% CI 1.1–1.7), postpartum hemorrhage (5.5% vs. 3.8%; HR 1.3, 95% CI 1.1–1.6), and venous thromboembolism (2.7% vs. 0.7%; HR 3.2, 95% CI 2.2–4.6). Arterial thrombotic events were not significantly different between groups. Pregnancies in patients with MPN are associated with significantly increased maternal, obstetric, and venous thrombotic complications, highlighting the need for multidisciplinary management and individualized thromboprophylaxis strategies.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07285-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099061","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":"Outcomes of down syndrome-related myeloid leukemia in Turkiye: a multicenter retrospective observational cohort study by the Turkish Pediatric Hematology Association","authors":"Yeter Düzenli Kar,&nbsp;Hale Ören,&nbsp;Melike Sezgin Evim,&nbsp;Emine Zengin,&nbsp;Ekin Gün,&nbsp;Nihal Karadaş,&nbsp;Deniz Yılmaz Karapınar,&nbsp;Canan Albayrak,&nbsp;Selma Ünal,&nbsp;Feryal Karahan,&nbsp;Murat Söker,&nbsp;Veysiye Hulya Uzel,&nbsp;Arzu Akyay,&nbsp;Yurday Öncül,&nbsp;Ayşenur Bahadır,&nbsp;Mehmet Fatih Orhan,&nbsp;Suar Çakı Kılıç,&nbsp;Burcu Tufan Taş,&nbsp;Elif Güler Kazancı,&nbsp;Betül Orhaner,&nbsp;Tuba Hilkay Karapınar,&nbsp;Yusuf Ziya Aral,&nbsp;Neşe Yaralı,&nbsp;Ali Fettah,&nbsp;Güven Özkaya,&nbsp;Adalet Meral Güneş","doi":"10.1007/s00277-026-07245-0","DOIUrl":"10.1007/s00277-026-07245-0","url":null,"abstract":"<div><p>Children with Down syndrome (DS) have a 150-times increased risk of myeloid leukemia (ML). In DS patients, in addition to DS-ML, common acute myeloid leukemia (AML) subtypes (standard-AML), observed in patients without DS, may also be seen. We evaluated ML types developing among DS cases, along with clinical features, survival, relapse, and mortality rates. The study included DS children aged 6 months to 18 years with newly diagnosed ML. Patients were classified retrospectively into two groups according to WHO guidelines and BFM-AML protocol recommendations as DS-ML and standard AML-DS. Among 53 DS patients, 71.7% (n = 38) had DS-ML and 28.3% (n = 15) had standard AML-DS. The mean age in the DS-ML group was significantly lower than the standard AML-DS group (23 ± 9 vs. 48 ± 51 months, p = 0.033). The 5-year overall survival (OS) and event-free survival (EFS) in the DS-ML group were 84.1%±6.0% and 81.3%±6.4%, respectively. For the standard AML, OS and EFS were 53.3%±12.9% and 45.7%±13.1%, respectively. The DS-ML group had significantly higher OS and EFS than the standard AML-DS group (p = 0.039 and p = 0.025, respectively). In our study, DS-ML and standard AML-DS were evaluated separately, which significantly contributes to the literature on the clinical and laboratory features of both groups, given the limited data on these topics. In the DS-ML group, complete remission, OS, and EFS were significantly higher than in the standard AML-DS. Differentiating DS-ML from standard AML-DS will ensure that patients with these biologically distinct diseases receive treatment of appropriate intensity and increase survival by reducing early mortality and relapse risk.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07245-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986496","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":"Early deep response to cilta-cel as 2nd CAR T-Cell therapy after CELMoD-based bridging for advanced multiple myeloma","authors":"Henrik Niklas,&nbsp;Anna Bold,&nbsp;Simon Völkl,&nbsp;Nicola Lang,&nbsp;Marietta Truger,&nbsp;Knut Wendelin,&nbsp;Susanne Strifler,&nbsp;Johannes Gärtner,&nbsp;Stefan Knop","doi":"10.1007/s00277-026-07278-5","DOIUrl":"10.1007/s00277-026-07278-5","url":null,"abstract":"<div><p>Abstract</p><p>Chimeric antigen receptor (CAR) T-cell therapy has emerged as an innovative and highly effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). This effect is based on redirecting modified T-cells towards plasma cells expressing target antigens, specifically B cell maturation antigen (BCMA). Despite high initial response rates, disease relapse remains a major clinical challenge. Therapeutic options after progression following prior BCMA-directed CAR T-cell therapy are limited, and prognosis is often poor. </p><p>We report on a 58-year-old male with high-risk IgA kappa multiple myeloma who was heavily pretreated and received idecabtagene vicleucel as sixth-line therapy, achieving a deep response lasting for approximately one year. Following disease progression, the patient received bridging therapy with mezigdomide,carfilzomib, and dexamethasone, followed by a second BCMA-directed CAR T-cell infusion using ciltacabtagene autoleucel. Previous whole genome sequencing had confirmed preserved BCMA expression.</p><p>Early post-infusion assessment showed a rapid and profound response, with marked declines in serum IgA and free kappa light chains, accompanied by robust CAR T-cell expansion. Treatment-related toxicities were manageable, including grade II cytokine release syndrome and prolonged cytopenias, without evidence of neurotoxicity.</p><p>This case provides additional knowledge that retreatment with BCMA-directed CAR T-cell therapy may be feasible and clinically effective in heavily pretreated multiple myeloma, particularly after a durable response to initial CAR T-cell therapy. Bridging therapy and the use of an alternative CAR T-cell construct may further improve outcomes. Prospective studies are needed to define optimal patient selection and treatment sequencing in this setting.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07278-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982183","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":"Possible CPX-351-associated drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome-like reaction during severe lymphopenia","authors":"Seiya Bamba,&nbsp;Junya Kanda,&nbsp;Misaki Hada,&nbsp;Yoshiharu Kubota,&nbsp;Saeko Nakajima,&nbsp;Takashi Nomura,&nbsp;Takuto Fukutome,&nbsp;Kentaro Tsuji,&nbsp;Akifumi Takaori-Kondo","doi":"10.1007/s00277-026-07282-9","DOIUrl":"10.1007/s00277-026-07282-9","url":null,"abstract":"<div><p>Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe delayed drug reaction characterized by skin eruption, systemic inflammation, organ involvement, and human herpesvirus 6 (HHV-6) reactivation. CPX-351 is increasingly used for high-risk acute myeloid leukemia, and skin eruptions are common adverse events; however, CPX-351-associated DRESS/DIHS-like reactions have not been well described. We report a 62-year-old man with acute erythroid leukemia who developed a progressive eruption after CPX-351 therapy. An early intertriginous and truncal eruption was initially compatible with toxic erythema of chemotherapy (TEC), whereas subsequent recurrent fever, generalized erythema involving more than 90% of the body surface area, lymphadenopathy, atypical lymphocytes, liver enzyme elevation, and marked HHV-6 DNA elevation (1.2 × 10⁶ copies/mL) supported the diagnosis of a DRESS/DIHS-like reaction. The reaction occurred despite severe lymphopenia, absence of peripheral eosinophilia, inconspicuous dermal eosinophils, and a normal serum thymus and activation-regulated chemokine level. Skin biopsy showed interface dermatitis with superficial perivascular lymphocytic infiltration. Systemic prednisolone led to rapid defervescence, improvement of appetite and skin lesions, disappearance of atypical lymphocytes, and clearance of HHV-6 DNA. The patient subsequently underwent conditioning and umbilical cord blood transplantation. CPX-351 was considered a possible culprit based on the temporal relationship, although TEC and concomitant medications represented important alternative considerations. This case suggests that a DRESS/DIHS-like reaction can develop in severely immunocompromised patients and that HHV-6 reactivation may help identify this condition when eosinophilia is absent.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07282-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189834","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":"Presenting a multi-marker response-adapted framework for venetoclax duration in acute myeloid leukemia","authors":"Nabiha Adnan","doi":"10.1007/s00277-026-07280-x","DOIUrl":"10.1007/s00277-026-07280-x","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962896","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":"Apoptosis gene expression analysis identifies biologically distinct AML clusters and BIK as an independent prognostic marker","authors":"Kinga Strzałka,&nbsp;Piotr Strzałka,&nbsp;Dariusz Jarych,&nbsp;Aneta Wiśnik,&nbsp;Damian Mikulski,&nbsp;Kacper Kościelny,&nbsp;Magdalena Czemerska,&nbsp;Izabela Zawlik,&nbsp;Agnieszka Wierzbowska,&nbsp;Agnieszka Pluta","doi":"10.1007/s00277-026-07268-7","DOIUrl":"10.1007/s00277-026-07268-7","url":null,"abstract":"<div><p>Dysregulation of apoptosis is a key feature of acute myeloid leukemia (AML) and contributes to therapy resistance, yet the clinical relevance of apoptosis-related gene expression remains incompletely understood. We prospectively analyzed mRNA expression of apoptosis-related genes in bone marrow mononuclear cells from 90 newly diagnosed AML patients. Gene expression clustering identified two biologically distinct patient groups. The subgroup with significantly inferior overall survival (Cluster 2) showed coordinated upregulation of pro-apoptotic genes, including <i>BCL2L11 (BIM)</i>,<i> BBC3 (PUMA)</i>,<i> BID</i>,<i> BAD</i>,<i> BIK</i>, and <i>BAX</i>, together with a shift in anti-apoptotic signaling toward lower <i>BCL2</i> expression and increased expression of alternative survival regulators, <i>MCL1</i> and <i>BCL2L1 (BCL-xL)</i>. Reduced expression of executioner caspases <i>CASP3</i> and <i>CASP7</i> was also observed in Cluster 2, which may indicate less efficient apoptotic execution. Among patients treated with venetoclax + azacitidine (VenAza), Cluster 2 demonstrated significantly shorter event-free survival. This finding is consistent with the biological features of Cluster 2, including a monocytic immunophenotype previously associated with reduced sensitivity to BCL-2–targeted therapy and increased reliance on alternative anti-apoptotic regulators such as MCL1 and BCL-xL. Analysis of individual genes showed that higher <i>BIK</i> mRNA expression was associated with poorer survival and lack of response to VenAza, highlighting the paradoxical association between increased expression of this pro-apoptotic gene and adverse clinical outcome. These findings demonstrate that dysregulation of apoptosis-related gene expression defines clinically distinct AML subgroups and may contribute to differences in prognosis and therapeutic response.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164846","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}