HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.286331
Roberta Soscia, Giovanni Manfredi Assanto, Irene Della Starza, Riccardo Moia, Donatella Talotta, Vittorio Bellomarino, Teresa Bellissimo, Marco Antonacci, Luigi Petrucci, Gianluca Gaidano, Anna Guarini, Maurizio Martelli, Alice Di Rocco, Robin Foà, Ilaria Del Giudice
{"title":"Molecular measurable residual disease by immunoglobulin gene rearrangements on circulating tumor DNA predicts outcome in diffuse large B-cell lymphoma.","authors":"Roberta Soscia, Giovanni Manfredi Assanto, Irene Della Starza, Riccardo Moia, Donatella Talotta, Vittorio Bellomarino, Teresa Bellissimo, Marco Antonacci, Luigi Petrucci, Gianluca Gaidano, Anna Guarini, Maurizio Martelli, Alice Di Rocco, Robin Foà, Ilaria Del Giudice","doi":"10.3324/haematol.2024.286331","DOIUrl":"10.3324/haematol.2024.286331","url":null,"abstract":"<p><p>In diffuse large B-cell lymphoma (DLBCL) treatment response relies on imaging. We investigated the potential value of molecular measurable residual disease (MRD) on circulating tumor DNA (ctDNA) to predict the outcome of 73 DLBCL patients. At baseline, next-generation sequencing was used to detect clonal immunoglobulin (IG) gene rearrangements on tumor biopsies (N=57) and ctDNA (N=73). MRD monitoring was applied by tracking the IG clones in ctDNA samples collected during treatment (interim) and at the end of treatment (EOT). MRD results were correlated with clinical data and radiologic disease assessment. Before treatment, clonal IG were found in 91.2% (52/57) of tumor biopsies and in 93.2% (68/73) of ctDNA samples. In paired samples, the same clonotype was found in 69.2% (36/52) of cases. At the interim analysis, ctDNA MRD was negative in 32 of 45 evaluable patients and positive in 13 of 45, correlating significantly with progression-free survival (PFS) (78.1% MRD- vs. 30.8% MRD+; P<0.0001) after a median follow-up of 40 months. Moreover, ctDNA MRD could stratify prognosis of 27 patients in partial response (P=0.018). At EOT, ctDNA MRD was negative in 37 of 47 patients and positive in ten of 47 (PFS 83.8% MRD- vs. 0% MRD+; P<0.0001). All MRD+ patients in complete metabolic response relapsed (P<0.0001). At multivariate analysis, MRD at EOT independently predicted PFS and overall survival. Monitoring IG-based ctDNA MRD during and after treatment predicts DLBCL patients' outcome. This non-invasive method should be implemented in risk-adapted clinical trials and validated as a treatment decision-making tool.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1573-1583"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.285826
Anna Torun, Aleksandra Zdanowicz, Nina Miazek-Zapala, Piotr Zapala, Bhaskar Pradhan, Marta Jedrzejczyk, Andrzej Ciechanowicz, Zofia Pilch, Marcin Skorzynski, Mikołaj Słabicki, Grzegorz Rymkiewicz, Joanna Barankiewicz, Claudio Martines, Luca Laurenti, Marta Struga, Magdalena Winiarska, Jakub Golab, Magdalena Kucia, Mariusz Z Ratajczak, Adam Huczynski, Dinis P Calado, Dimitar G Efremov, Abdessamad Zerrouqi, Beata Pyrzynska
{"title":"Potassium/sodium cation carriers robustly upregulate CD20 antigen by targeting MYC, and synergize with anti- CD20 immunotherapies to eliminate malignant B cells.","authors":"Anna Torun, Aleksandra Zdanowicz, Nina Miazek-Zapala, Piotr Zapala, Bhaskar Pradhan, Marta Jedrzejczyk, Andrzej Ciechanowicz, Zofia Pilch, Marcin Skorzynski, Mikołaj Słabicki, Grzegorz Rymkiewicz, Joanna Barankiewicz, Claudio Martines, Luca Laurenti, Marta Struga, Magdalena Winiarska, Jakub Golab, Magdalena Kucia, Mariusz Z Ratajczak, Adam Huczynski, Dinis P Calado, Dimitar G Efremov, Abdessamad Zerrouqi, Beata Pyrzynska","doi":"10.3324/haematol.2024.285826","DOIUrl":"10.3324/haematol.2024.285826","url":null,"abstract":"<p><p>Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/ sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 chimeric antigen receptor T cells, significantly improving non-Hodgkin lymphoma therapy. The results of RNA sequencing, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat non-Hodgkin lymphoma and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1555-1572"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.285154
Serena De Matteis, Laura Del Coco, Federica De Castro, Anna Maria Giudetti, Beatrice Casadei, Francesco Iannotta, Francesco De Felice, Enrica Tomassini, Francesca Vaglio, Maria Naddeo, Irene Salamon, Gianluca Storci, Noemi Laprovitera, Daria Messelodi, Salvatore Nicola Bertuccio, Marta Tassoni, Barbara Sinigaglia, Francesco Barbato, Margherita Ursi, Elena Campanini, Enrico Maffini, Marcello Roberto, Cinzia Pellegrini, Elisa Dan, Chiara Pirazzini, Paolo Garagnani, Manuela Ferracin, Pier Luigi Zinzani, Francesco Paolo Fanizzi, Massimiliano Bonafè, Francesca Bonifazi
{"title":"Metabolic profile evolution in relapsed/refractory B-cell non-Hodgkin lymphoma patients treated with CD19 chimeric antigen receptor T-cell therapy and implications in clinical outcome.","authors":"Serena De Matteis, Laura Del Coco, Federica De Castro, Anna Maria Giudetti, Beatrice Casadei, Francesco Iannotta, Francesco De Felice, Enrica Tomassini, Francesca Vaglio, Maria Naddeo, Irene Salamon, Gianluca Storci, Noemi Laprovitera, Daria Messelodi, Salvatore Nicola Bertuccio, Marta Tassoni, Barbara Sinigaglia, Francesco Barbato, Margherita Ursi, Elena Campanini, Enrico Maffini, Marcello Roberto, Cinzia Pellegrini, Elisa Dan, Chiara Pirazzini, Paolo Garagnani, Manuela Ferracin, Pier Luigi Zinzani, Francesco Paolo Fanizzi, Massimiliano Bonafè, Francesca Bonifazi","doi":"10.3324/haematol.2024.285154","DOIUrl":"10.3324/haematol.2024.285154","url":null,"abstract":"<p><p>Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/BNHL) infused with approved CD19 chimeric antigen receptor (CAR) T-cell products at the time of pre-lymphodepletion (PLD) and at day +1 (D1), D7, and D30 after CAR T-cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At D1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel-compared to axi-cel-treated patients. At D30, discriminant analysis found two clusters in a subgroup of patients, one with complete response lasting 1 year after therapy, and another who relapsed within 1 year (relapsed >D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR T-cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR T patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1545-1554"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-02-13DOI: 10.3324/haematol.2024.287062
Cyril Salek, Stepan Hrabovsky, Frantisek Folber, Zdenek Koristek, Jan M Horacek, Eva Fronkova, Leona Rezkova Reznickova, Pavla Pecherkova, Petr Soukup, Barbora Dluhosova, Vaclava Polivkova, Jitka Krizkova, Katerina Machova Polakova, Zuzana Vrzalova, Hana Halamova, Jan Trka, Petr Cetkovsky, Michael Doubek
{"title":"Blinatumomab in induction therapy improves molecular response in untreated adults with Ph- B-cell precursor acute lymphoblastic leukemia.","authors":"Cyril Salek, Stepan Hrabovsky, Frantisek Folber, Zdenek Koristek, Jan M Horacek, Eva Fronkova, Leona Rezkova Reznickova, Pavla Pecherkova, Petr Soukup, Barbora Dluhosova, Vaclava Polivkova, Jitka Krizkova, Katerina Machova Polakova, Zuzana Vrzalova, Hana Halamova, Jan Trka, Petr Cetkovsky, Michael Doubek","doi":"10.3324/haematol.2024.287062","DOIUrl":"10.3324/haematol.2024.287062","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1644-1648"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-03-06DOI: 10.3324/haematol.2024.286424
Larissa Lordier, Christian A Di Buduo, Alexandre Kauskot, Nathalie Balayn, Cécile Lavenu-Bombled, Francesco Baschieri, Valérie Proulle, Cecilia P Marin Oyarzun, Francesca Careddu, Ida Biunno, Tudor Manoliu, Philippe Rameau, Isabelle Plo, Nicolas Papadopoulos, Stefan Constantinescu, William Vainchenker, Guillaume Nam Nguyen, Paola Ballerini, Remi Favier, Alessandra Balduini, Hana Raslova
{"title":"Increased RhoA pathway activation downstream of αIIbβ3/SRC contributes to heterozygous Bernard Soulier syndrome.","authors":"Larissa Lordier, Christian A Di Buduo, Alexandre Kauskot, Nathalie Balayn, Cécile Lavenu-Bombled, Francesco Baschieri, Valérie Proulle, Cecilia P Marin Oyarzun, Francesca Careddu, Ida Biunno, Tudor Manoliu, Philippe Rameau, Isabelle Plo, Nicolas Papadopoulos, Stefan Constantinescu, William Vainchenker, Guillaume Nam Nguyen, Paola Ballerini, Remi Favier, Alessandra Balduini, Hana Raslova","doi":"10.3324/haematol.2024.286424","DOIUrl":"10.3324/haematol.2024.286424","url":null,"abstract":"<p><p>Bernard Soulier syndrome (BSS) is a severe bleeding disorder with moderate to severe thrombocytopenia, giant platelets, and platelet dysfunction, caused by biallelic mutations in GP1BA, GP1BB, or GP9 genes. We generated induced pluripotent stem cells (iPSC) from a BSS patient with a novel heterozygous GP1BA p.N103D mutation, resulting in moderate macrothrombocytopenia. The mutation does not affect megakaryocyte (MK) differentiation or GPIb-GPIX complex expression but reduces affinity to von Willebrand factor (VWF). It induces increased signaling independent of VWF and αIIbβ3-mediated outside-in signaling, causing a profound defect in proplatelet formation after adhesion on fibrinogen. Pre-activation of αIIbβ3 integrin and heightened stress fiber formation linked to RhoA pathway overactivation were observed, likely due to increased phosphorylation of SRC at Y419 downstream of GPIbα. Dasatinib, a SRC inhibitor, restored stress fiber formation. Using a 3D bone marrow model to mimic platelet release under flow, we demonstrated that the ROCK1/2 inhibitor Y27632 increased platelet number and restored platelet size in GPIbαN103D MK, as well as in MK from two other patients with heterozygous GP1BA mutations (p.L160P and p.N150S). However, Y27632 had no additional effect on platelet generation from MK of two patients with biallelic BSS, suggesting a distinct molecular mechanism in biallelic cases.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1596-1609"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-12DOI: 10.3324/haematol.2024.286152
Silvia García Adrián, Claudia Iglesias Pérez, Alberto Carmona-Bayonas, Laura Ortega Morán, Jaime Rubio Pérez, Purificación Martínez Del Prado, Eva Martínez De Castro, Fernando Neria, Isaura Fernández Pérez, Marta García De Herreros, Marta Carmona Campos, Ignacio García Escobar, Rut Porta Balanyà, David Marrupe González, Paula Jiménez Fonseca, María Esperanza Guirao García, Manuel Sánchez Cánovas, José Muñoz Langa, Pedro Pérez Segura, Ma José Méndez Vidal, Andrés J Muñoz Martín, Spanish Society Of Medical Oncology
{"title":"Cancer-related thrombosis: impact of biological sex on the risk of rethrombosis and bleeding.","authors":"Silvia García Adrián, Claudia Iglesias Pérez, Alberto Carmona-Bayonas, Laura Ortega Morán, Jaime Rubio Pérez, Purificación Martínez Del Prado, Eva Martínez De Castro, Fernando Neria, Isaura Fernández Pérez, Marta García De Herreros, Marta Carmona Campos, Ignacio García Escobar, Rut Porta Balanyà, David Marrupe González, Paula Jiménez Fonseca, María Esperanza Guirao García, Manuel Sánchez Cánovas, José Muñoz Langa, Pedro Pérez Segura, Ma José Méndez Vidal, Andrés J Muñoz Martín, Spanish Society Of Medical Oncology","doi":"10.3324/haematol.2024.286152","DOIUrl":"10.3324/haematol.2024.286152","url":null,"abstract":"<p><p>Patients with cancer have a higher risk of re-thrombosis and bleeding secondary to anticoagulant treatment than have individuals without cancer. Given the lack of specific clinical trials, the decision regarding the optimal duration of treatment must consider multiple factors, including sex. The current study used data from the international, prospective TESEO Registry that includes consecutive patients diagnosed with cancer-associated thrombosis. Between July 2018 and December 2022, 2,823 patients were included in the TESEO Registry, 1,351 (48%) of whom were female. The most common venous thromboembolic event (VTE) in both sexes was pulmonary embolism, with an incidence of 58.0% among men and 54.3% in women (P=0.045). After a median follow-up of 6.9 months (interquartile range, 1.9-14.4), the re-thrombosis rate at the end of follow-up was 10.0% in males and 15.0% in females (P=0.14). The location of the primary tumor in the gastrointestinal tract was associated with a greater risk of re-thrombosis, whereas sex had no significant impact. Men had twice as many major bleeds. Additional risk factors for major bleeding included situations of risk due to tumor site or thrombocytopenia, as well as the presence of active tumor bleeding at the time of VTE diagnosis. Overall survival was longer among women. Given the higher incidence of major bleeding among men, sex should be deemed a relevant factor when deciding the duration of anticoagulant treatment in cancer patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1513-1522"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-02-06DOI: 10.3324/haematol.2024.286695
Matthew Schwede, Gladys Rodriguez, Vanessa E Kennedy, Solomon Henry, Douglas Wood, Gabriel N Mannis, Ravindra Majeti, Jonathan H Chen, Eran Bendavid, Tian Yi Zhang
{"title":"The improved prognosis of <i>FLT3</i>-internal tandem duplication but not tyrosine kinase domain mutations in acute myeloid leukemia in the era of targeted therapy: a real-world study using large-scale electronic health record data.","authors":"Matthew Schwede, Gladys Rodriguez, Vanessa E Kennedy, Solomon Henry, Douglas Wood, Gabriel N Mannis, Ravindra Majeti, Jonathan H Chen, Eran Bendavid, Tian Yi Zhang","doi":"10.3324/haematol.2024.286695","DOIUrl":"10.3324/haematol.2024.286695","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1634-1638"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-02-13DOI: 10.3324/haematol.2024.285572
Sunil K Joshi, Ariane Huang, Janét Pittsenbarger, Ujwal Shinde, Camilo Posso, Paul D Piehowski, Sara J C Gosline, Richard D Press, Marina A Gritsenko, Chelsea Hutchinson, Karl K Weitz, Kevin Watanabe-Smith, Nicola Long, Karin D Rodland, Jeffrey W Tyner, Brian J Druker, Cristina E Tognon
{"title":"Oncogenic <i>NTRK3</i> mutations exhibit differential sensitivity to tropomyosin receptor kinase inhibitors in patients with acute myeloid leukemia.","authors":"Sunil K Joshi, Ariane Huang, Janét Pittsenbarger, Ujwal Shinde, Camilo Posso, Paul D Piehowski, Sara J C Gosline, Richard D Press, Marina A Gritsenko, Chelsea Hutchinson, Karl K Weitz, Kevin Watanabe-Smith, Nicola Long, Karin D Rodland, Jeffrey W Tyner, Brian J Druker, Cristina E Tognon","doi":"10.3324/haematol.2024.285572","DOIUrl":"10.3324/haematol.2024.285572","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1616-1622"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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