Blood Neoplasia最新文献

{"title":"Analyses of transplantation outcomes for adult patients with mixed-phenotype acute leukemia","authors":"Tomoyasu Jo ,&nbsp;Tadakazu Kondo ,&nbsp;Shohei Mizuno ,&nbsp;Shinichi Kako ,&nbsp;Noriko Doki ,&nbsp;Naoyuki Uchida ,&nbsp;Masatsugu Tanaka ,&nbsp;Tetsuya Nishida ,&nbsp;Takahiro Fukuda ,&nbsp;Masashi Sawa ,&nbsp;Yoshinobu Kanda ,&nbsp;Satoru Takada ,&nbsp;Yuta Hasegawa ,&nbsp;Yuta Katayama ,&nbsp;Satoshi Yoshihara ,&nbsp;Koji Kawamura ,&nbsp;Marie Ohbiki ,&nbsp;Yoshiko Atsuta ,&nbsp;Masamitsu Yanada ,&nbsp;Yasuyuki Arai","doi":"10.1016/j.bneo.2025.100166","DOIUrl":"10.1016/j.bneo.2025.100166","url":null,"abstract":"<div><h3>Abstract</h3><div>Mixed-phenotype acute leukemia (MPAL) is associated with poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can achieve long-term survival, optimal transplantation strategies remain unclear. We analyzed a national registry of adult patients with MPAL who underwent allo-HSCT between 2008 and 2022 in Japan. Among 417 patients, median age at transplant was 44 years (interquartile range, 32-55); 61% were male, 20% were <em>BCR::ABL1</em>-positive, and 66% underwent transplant during the first complete remission (CR; CR1). At 5 years posttransplant, overall survival (OS) was 54%, disease-free survival was 49%, relapse was 28%, and nonrelapse mortality was 23%. Multivariate analysis identified older age (adjusted hazard ratio [aHR], 1.78 [95% confidence interval (CI), 1.11-2.84] for ages 50-59 years; aHR, 2.65 [95% CI, 1.54-4.55] for ≥60 years; both vs &lt;40 years), male sex (aHR, 1.56; 95% CI, 1.07-2.27), Eastern Cooperative Oncology Group performance status scale ≥2 (aHR, 3.05; 95% CI, 1.72-5.40), <em>BCR::ABL1</em> -negative status (aHR, 1.64; 95% CI, 1.02-2.64), advanced disease status (aHR, 1.642 [95% CI, 0.80-3.36] for second CR; aHR, 4.01 [95% CI, 2.61-6.15] for third or higher CR, or non-CR vs CR1), and low conditioning intensity (aHR, 2.49 [95% CI, 1.21-5.13] for low transplant conditioning intensity [TCI] vs high TCI) as adverse prognostic factors for OS. A propensity score–matched comparison with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) during the same period showed that MPAL did not have significantly worse prognosis than AML or ALL. These findings suggest that allo-HSCT offers long-term survival in MPAL, with outcomes not inferior to those of AML and ALL.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posttransplant rituximab exposure and risk of PTLD in solid organ transplant recipients with EBV DNAemia","authors":"Evelyn H. Orlando ∗ ,&nbsp;Patrick Gould ∗ ,&nbsp;Brian Cuzzo ,&nbsp;Maegan Ford ,&nbsp;Yuxuan Chen ,&nbsp;Alexander Sanjurjo ,&nbsp;Saagar Jain ,&nbsp;Benjamin May ,&nbsp;Demetra Tsapepas ,&nbsp;Rebecca J. Leeman-Neill ,&nbsp;Govind Bhagat ,&nbsp;Geoffrey K. Dube ,&nbsp;Heather Morris ,&nbsp;Selim Arcasoy ,&nbsp;Farhana Latif ,&nbsp;Ersilia M. DeFilippis ,&nbsp;Mercedes Martinez ,&nbsp;Gene Y. Im ,&nbsp;Meaghan M. Phipps ,&nbsp;Marcus R. Pereira ,&nbsp;Jennifer E. Amengual †","doi":"10.1016/j.bneo.2025.100160","DOIUrl":"10.1016/j.bneo.2025.100160","url":null,"abstract":"<div><h3>Abstract</h3><div>The association between Epstein-Barr virus (EBV) DNAemia after solid organ transplantation (SOT) and posttransplant lymphoproliferative disorder (PTLD) is well described. Published data support preemptive rituximab for EBV DNAemia after bone marrow transplant. However, there are inadequate data to support any specific preemptive strategy for DNAemia after SOT. The goal of this single-center retrospective cohort study was to explore the association between posttransplant rituximab and development of PTLD in SOT recipients with EBV DNAemia. This study included 1386 patients with EBV DNAemia after SOT at Columbia University Irving Medical Center from 2008 to 2023. There were 129 patients who received rituximab for various indications (eg, organ rejection, EBV DNAemia). Across all patients, 82 of 1386 (6%) developed PTLD and the 5-year PTLD-free survival rate was 95%. In multivariable analysis, posttransplant rituximab exposure for any indication was independently associated with a reduced rate of PTLD over time as a time-independent (hazard ratio [HR], 0.16; <em>P</em> = .011) but not time-dependent (HR, 0.25; <em>P</em> = .056) variable. When limiting the rituximab-exposed cohort to the 60 patients who received rituximab after documented EBV DNAemia, time-independent (HR, 0.25; <em>P</em> = .06) and time-dependent (HR, 0.43; <em>P</em> = .2) rituximab exposure were not associated with PTLD-free survival. Higher EBV peak viral load, high-risk organ transplant type, and high-risk EBV serostatus were independently associated with increased rates of PTLD. This retrospective study suggests that posttransplant rituximab may reduce the rate of PTLD in SOT recipients. Prospective, randomized studies are needed to more rigorously determine the benefit of preemptive rituximab for the prevention of PTLD in patients with EBV DNAemia.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orally available decitabine prodrug OR-2100 induces mitotic perturbation for the treatment of double-hit lymphoma","authors":"Keisuke Kidoguchi ,&nbsp;Hiroshi Ureshino ,&nbsp;Yuta Yamamoto ,&nbsp;Ryo Yanagiya ,&nbsp;Yuki Kurahashi ,&nbsp;Yuki Fukuda-Kurahasi ,&nbsp;Yumeka Mine ,&nbsp;Shigehisa Aoki ,&nbsp;Kazutaka Nakashima ,&nbsp;Hiroaki Miyoshi ,&nbsp;Koichi Ohshima ,&nbsp;Atsushi Kawaguchi ,&nbsp;Shinya Kimura","doi":"10.1016/j.bneo.2025.100155","DOIUrl":"10.1016/j.bneo.2025.100155","url":null,"abstract":"<div><h3>Abstract</h3><div>Double-hit lymphoma (DHL), an aggressive B-cell lymphoma with a poor prognosis, harbors rearrangements of <em>MYC</em> and <em>BCL2</em>. The standard chemoimmunotherapy comprising R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) yields an unsatisfactory treatment response. Hypomethylating agents increase the susceptibility to malignant lymphoma via the restoration of tumor suppressor genes. Decitabine not only inhibits DNA methylation but also causes mitotic disruption, which leads to antileukemia effects through the covalent binding of DNA methyltransferase 1 to DNA. Previously, we developed an orally bioavailable prodrug of decitabine (OR-2100). Here, we investigated the efficacy and underlying mechanism of OR-2100 as a treatment for DHL. OR-2100 alone or in combination with key antilymphoma drugs, including doxorubicin and vincristine, suppressed the in vitro proliferation of DHL cell lines, particularly those with wild-type <em>TP53</em>. OR-2100 induced downregulation of <em>CDCA8</em> and <em>BIRC5</em> (baculoviral IAP [inhibitor of apoptosis] repeat–containing 5), the knockdown of which suppressed the proliferation of DHL cell lines. Both OR-2100 treatment and <em>CDCA8</em> knockdown led to mitotic perturbation, suggesting that the disruption of mitosis may underlie the antitumor mechanism of OR-2100 given that the efficacy of OR-2100 was dependent on the <em>TP53</em> status and that <em>CDCA8</em> and <em>BIRC5</em> are downstream targets of the E2F1 pathway. These findings suggest that the antitumor activity of OR-2100 may be mediated through inhibition of the E2F1 pathway. The combination of CHOP and OR-2100 reduced the tumor weight significantly in a xenograft mouse model without increased toxicities. The induction of mitotic perturbation might be a key antilymphoma mechanism for OR-2100, and the combination of OR-2100 and CHOP might be a promising treatment strategy for DHL.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ivosidenib or venetoclax combined with hypomethylating agents in IDH1-mutated acute myeloid leukemia: a real-world study","authors":"Curtis A. Lachowiez ,&nbsp;B. Douglas Smith ,&nbsp;Alexander Joseph Ambinder ,&nbsp;Gary Binder ,&nbsp;Anne Angiolillo ,&nbsp;Ravi Potluri ,&nbsp;Eros Papademetriou ,&nbsp;Thomas W. LeBlanc","doi":"10.1016/j.bneo.2025.100152","DOIUrl":"10.1016/j.bneo.2025.100152","url":null,"abstract":"<div><h3>Abstract</h3><div>Approximately 10% of patients with newly diagnosed acute myeloid leukemia (ND-AML) harbor the isocitrate dehydrogenase 1 gene mutation (m<em>IDH1</em>). In this real-world study evaluating ivosidenib (IVO) + hypomethylating agents (HMAs; n = 181) vs venetoclax (VEN) + HMAs (n = 99) in patients with m<em>IDH1</em> ND-AML, those treated with IVO+HMA had higher rates of complete remission (CR; 42.5% vs 26.3%; <em>P</em> = .007), higher rates of composite CR + CR with incomplete platelet count recovery (63.0% vs 48.5%; <em>P</em> = .019), shorter median time to best response (3.3 vs 4.1 months; <em>P</em> = .006), and improved 6-month event-free survival (55.8% vs 38.4%; <em>P</em> = .006). Most patients treated with VEN received well under 28 days of VEN per cycle, likely due to anticipation of toxicity; outcomes with this short-schedule VEN were proportionately worse with fewer days of exposure per cycle. The between-group rate of grade ≥3 adverse events was similar within 30 days of treatment initiation, except for higher rates of febrile neutropenia for VEN+HMA vs IVO+HMA (8.1% vs 1.7%; <em>P</em> = .008). These findings support results from the phase 3 AGILE trial demonstrating IVO+HMA’s efficacy and favorable toxicity profile in patients with m<em>IDH1</em> ND-AML. IVO + azacitidine should be considered as the preferred standard of care treatment regimen in this patient subgroup.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of STAT3 in acute myeloid leukemia favors tissue infiltration linked to CXCR4 signaling","authors":"Bernhard Zdársky ,&nbsp;Sophie Edtmayer ,&nbsp;Agnieszka Witalisz-Siepracka ,&nbsp;Stefanie Weiss ,&nbsp;Stefanie Boigenzahn ,&nbsp;Kerstin Heindl ,&nbsp;Safia Zahma ,&nbsp;Balázs Győrffy ,&nbsp;Richard Moriggl ,&nbsp;Dagmar Stoiber","doi":"10.1016/j.bneo.2025.100158","DOIUrl":"10.1016/j.bneo.2025.100158","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-mediated trogocytosis as a new mechanism of action of daratumumab","authors":"Mauro Lorenzo-Mohamed ∗ ,&nbsp;Carla Vicario-Bueno ∗ ,&nbsp;Andrea Díaz-Tejedor ,&nbsp;Marta González-Rodríguez ,&nbsp;Bárbara Castellanos ,&nbsp;Janet Sotolongo-Ravelo ,&nbsp;Laura San-Segundo ,&nbsp;Lorena González-Méndez ,&nbsp;Montserrat Martín-Sánchez ,&nbsp;Mercedes Garayoa ,&nbsp;Teresa Paíno","doi":"10.1016/j.bneo.2025.100151","DOIUrl":"10.1016/j.bneo.2025.100151","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in ALPINE: a secondary analysis","authors":"June-Wha Rhee ∗ ,&nbsp;Nicole Lamanna ∗ ,&nbsp;Wassim Aldairy ,&nbsp;Lipeng Chen ,&nbsp;Jun Zhang ,&nbsp;Dulce Ramirez ,&nbsp;William B. White","doi":"10.1016/j.bneo.2025.100150","DOIUrl":"10.1016/j.bneo.2025.100150","url":null,"abstract":"<div><h3>Abstract</h3><div>Hypertension is a common side effect of Bruton tyrosine kinase inhibitors (BTKis). The second-generation BTKi zanubrutinib has high BTK selectivity, which may minimize off-target effects. A phase 3 trial (ALPINE) demonstrated improved efficacy and safety of zanubrutinib vs ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). To better understand hypertension risk with zanubrutinib vs ibrutinib in ALPINE, this post hoc analysis evaluated hypertension development by measuring antihypertensive therapy initiation. Eligible adults with R/R CLL/SLL were randomized to zanubrutinib 160 mg twice-a-day or ibrutinib 420 mg daily until disease progression/unacceptable toxicity. Differences in treatment-emergent hypertension, antihypertensive therapy use and changes in blood pressure were evaluated. Of 648 patients (zanubrutinib, n = 324; ibrutinib, n = 324), nearly half used antihypertensive therapy at baseline (zanubrutinib, 48%; ibrutinib, 45%). With zanubrutinib vs ibrutinib, initiation of a new antihypertensive agent (28% vs 32%) or new antihypertensive class (24% vs 29%) were comparable. In patients without baseline antihypertensive therapy, 21% vs 29% with zanubrutinib vs ibrutinib, respectively, initiated new antihypertensive therapy. In all patients, time-to-initiation of a new antihypertensive class was longer with zanubrutinib vs ibrutinib; in those without baseline antihypertensive therapy, time-to-initiation of a new antihypertensive agent was also longer. Mean systolic blood pressure changes were lower with zanubrutinib vs ibrutinib. In conclusion, zanubrutinib was associated with longer time to initiation of antihypertensive therapy compared with ibrutinib in ALPINE. These findings could be of clinical importance when initiating BTKi therapy in patients with CLL/SLL. This trial was registered at <span><span>www.ClinicalTrials.gov</span><svg><path></path></svg></span> as #NCT03734016.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MNT: a new target for AML","authors":"Karla C. Fischer ,&nbsp;Veronique Litalien ,&nbsp;Sarah T. Diepstraten ,&nbsp;Michelle Jahja ,&nbsp;Fiona C. Brown ,&nbsp;Gemma L. Kelly ,&nbsp;Andrew H. Wei ,&nbsp;Suzanne Cory","doi":"10.1016/j.bneo.2025.100149","DOIUrl":"10.1016/j.bneo.2025.100149","url":null,"abstract":"<div><h3>Abstract</h3><div>Deregulated expression of the transcription factor c-MYC is well established as a primary driver of diverse tumor types. In this study, for the first time to our knowledge, we show that mouse and human myeloid leukemias provoked by oncogenic mixed lineage leukemia (MLL) fusion proteins are dependent on the MYC family member MNT (MAX network transcriptional repressor), which is highly expressed in these AMLs. To investigate the role of MNT, we generated <em>Mnt-</em>deletable murine <em>MLL::AF9</em> acute myeloid leukemias (AMLs), using the well-studied hemopoietic reconstitution model. <em>Mnt</em> deletion provoked the apoptosis of <em>MLL::AF9</em> AML cells in vitro and increased apoptosis elicited by the BH3 (BCL-2 homology region 3) mimetic drugs S63845 (MCL-1 (Myeloid cell leukemia-1) specific), ABT-199/Venetoclax (BCL-2 (B-cell lymphoma-2) specific), and A-1331852 (BCL-X_L (B-cell lymphoma-extra large) specific). Remarkably, by inducing <em>Mnt</em> deletion in vivo in transplanted <em>MLL::AF9</em> AMLs, we significantly extended the survival of transplant recipients (<em>P</em> &lt; .0001), 50% of which became leukemia free. Using inducible CRISPR/Cas9, we also showed that 3 of 4 human AML cell lines were more potently killed in vitro by BH3 mimetic drugs after <em>MNT</em> deletion. Of note, inducing <em>MNT</em> deletion in a human <em>MLL-</em>rearranged AML cell line transplanted into NSG (NOD SCID Gamma) mice debulked established leukemia and significantly extended the survival of transplant recipients. Taken together with previous studies that demonstrated a critical role for MNT in the development and sustained expansion of B and T lymphomas, our results suggest that a small molecule inhibiting MNT function may be a valuable therapeutic agent for myeloid and lymphoid malignancies.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bendamustine switches TNF receptor superfamily signal from a survival to a death signal in B-cell lymphomas","authors":"Kensuke Nakao ,&nbsp;Hiroshi Arima ,&nbsp;Yui Arakawa ,&nbsp;Tomoyasu Jo ,&nbsp;Yujuan Guo ,&nbsp;Iroha Morita ,&nbsp;Tomohiro Taya ,&nbsp;Toshio Kitawaki ,&nbsp;Akifumi Takaori-Kondo ,&nbsp;Momoko Nishikori","doi":"10.1016/j.bneo.2025.100157","DOIUrl":"10.1016/j.bneo.2025.100157","url":null,"abstract":"<div><h3>Abstract</h3><div>Bendamustine is one of the primary chemotherapeutic agents for the treatment of B-cell lymphomas, whereas its toxicity to T cells is associated with a high rate of infectious complications and a potential negative impact on subsequent immunotherapies. Bendamustine has previously been reported to be a potent in vitro inhibitor of HOIP, the catalytic subunit of the linear ubiquitin chain assembly complex (LUBAC). Because LUBAC functions as a checkpoint for tumor necrosis factor receptor superfamily (TNFRSF)–induced cell death, we hypothesized that bendamustine may have specific activity on the CD40 or BAFF-R signaling in B-cell lymphomas. In a cell culture assay, we found that bendamustine not only suppressed CD40L- and BAFF-driven NF-κB signaling in B-cell lymphomas but also induced higher cell death in the presence of these signals, a phenomenon not typical of other chemotherapeutic agents. Bendamustine resistance was shown to be driven by knockout of TRAF3, a mediator of CD40 and BAFF-R signaling. Importantly, the toxic effect of bendamustine on T cells was also found to be associated with another TNFRSF molecule, OX40. Pretreatment with an antibody blocking OX40-OX40L signaling attenuated bendamustine-induced T-cell depletion in mice, whereas preserving the cytotoxic effect of bendamustine on transplanted B-cell lymphoma. In conclusion, both the antilymphoma effect and the T-lymphopenia induced by bendamustine are associated with TNFRSF signaling, and the T-cell toxicity can be separately controlled by blocking OX40 signaling before bendamustine administration.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model","authors":"Tabish Hussain ,&nbsp;Matthew D. Bramble ,&nbsp;Bin Liu ,&nbsp;Martin C. Abba ,&nbsp;Marta Chesi ,&nbsp;C. Marcelo Aldaz","doi":"10.1016/j.bneo.2025.100153","DOIUrl":"10.1016/j.bneo.2025.100153","url":null,"abstract":"<div><h3>Abstract</h3><div>Deletions and translocations affecting <em>WWOX</em> accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that <em>Wwox</em> deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing <em>Cd19 Wwox</em> knockout (KO) with <em>Vk^∗MYC</em> myeloma model mice, we generated a model with concurrent <em>Wwox</em> deletion and <em>MYC</em> activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that <em>Vk^∗MYC:Wwox KO</em> mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138⁺ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon <em>Wwox</em> deletion in <em>Vk^∗MYC</em> mice. <em>Wwox KO</em> plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell–specific <em>Wwox</em> deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 4","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220796","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}