Haematologica最新文献

{"title":"The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival.","authors":"Vesna S Stanulović, Shorog Al Omair, Michelle A C Reed, Jennie Roberts, Sandeep Potluri, Taylor Fulton-Ward, Nancy Gudgeon, Emma L Bishop, Juliette Roels, Tracey A Perry, Sovan Sarkar, Guy Pratt, Tom Taghon, Sarah Dimeloe, Ulrich L Günther, Christian Ludwig, Maarten Hoogenkamp","doi":"10.3324/haematol.2023.283471","DOIUrl":"10.3324/haematol.2023.283471","url":null,"abstract":"<p><p>T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the tricarboxylic acid cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3505-3519"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histamine dihydrochloride and low-dose interleukin-2 has anti-leukemic efficacy in <i>NPM1</i>-mutated and myelomonocytic/monocytic acute myeloid leukemia.","authors":"Malin S Nilsson, Michael Fiegl, Wolfgang Hiddemann, Wolfgang R Sperr, Fredrik B Thorén, Anna Martner, Kristoffer Hellstrand","doi":"10.3324/haematol.2024.285342","DOIUrl":"10.3324/haematol.2024.285342","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3781-3784"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-transfection of murine NXPE2 and murine glycophorin A confers reactivity with Ter-119.","authors":"Gregory R Keele, Ariel M Hay, Nadia K Holness, Arijita Jash, Sarah E Ewald, Callan O'Connor, Matthew Vincent, Monika Dzieciatkowska, Angelo D'Alessandro, Gary A Churchill, James C Zimring","doi":"10.3324/haematol.2024.285168","DOIUrl":"10.3324/haematol.2024.285168","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3755-3759"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLT3 inhibitors potentially improve response rates in acute myeloid leukemia harboring t(6;9)(<i>DEK::NUP214</i>): the Mayo Clinic experience.","authors":"Clifford M Csizmar, Antoine N Saliba, Patricia T Greipp, Hassan Alkhateeb, Kebede H Begna, James M Foran, Naseema Gangat, William J Hogan, C Christopher Hook, Mark R Litzow, Abhishek A Mangaonkar, Jeanne M Palmer, Animesh Pardanani, Mithun V Shah, Ayalew Tefferi, Mehrdad Hefazi Torghabeh, Alexandra P Wolanskyj-Spinner, Mrinal M Patnaik, Scott H Kaufmann, Aref Al-Kali","doi":"10.3324/haematol.2024.285359","DOIUrl":"10.3324/haematol.2024.285359","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3785-3789"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426735","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}

{"title":"A targeted gene signature stratifying mediastinal gray zone lymphoma into classical Hodgkin lymphoma-like or primary mediastinal B-cell lymphoma-like subtypes.","authors":"Grazia Gargano, Maria Carmela Vegliante, Flavia Esposito, Susanna A Pappagallo, Elena Sabattini, Claudio Agostinelli, Stefano A Pileri, Valentina Tabanelli, Maurilio Ponzoni, Luisa Lorenzi, Fabio Facchetti, Arianna Di Napoli, Marco Lucioni, Marco Paulli, Lorenzo Leoncini, Stefano Lazzi, Stefano Ascani, Giuseppina Opinto, Gian Maria Zaccaria, Giacomo Volpe, Paolo Mondelli, Antonella Bucci, Laura Selicato, Antonio Negri, Giacomo Loseto, Felice Clemente, Anna Scattone, Alfredo F Zito, Luca Nassi, Nicoletta Del Buono, Attilio Guarini, Sabino Ciavarella","doi":"10.3324/haematol.2024.285266","DOIUrl":"10.3324/haematol.2024.285266","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3771-3775"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation.","authors":"Olaf Penack, Christophe Peczynski, William Boreland, Daniel Wolff, Ivan Moiseev, Hélène Schoemans, Christian Koenecke, Charlotte Graham, Zinaida Peric","doi":"10.3324/haematol.2023.284810","DOIUrl":"10.3324/haematol.2023.284810","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells are in standard clinical use to treat relapsed or refractory hematologic malignancies, such as non-Hodgkin lymphoma, multiple myeloma and acute lymphoblastic leukemia. Owing to the rapidly progressing field of CAR T-cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between European centers in prevention, diagnosis and management of short- and long-term complications. To capture the current CAR T-cell management among European Society for Blood and Marrow Transplantation (EBMT) centers and to determine the medical need and specific areas for future clinical research the EBMT Transplant Complications Working Party performed a survey among 227 EBMT CAR T-cell centers. We received complete servey answers from 106 centers (47%) addressing questions in the areas of product selection, CAR T-cell logistics, management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome as well as management in later phases including prolonged cytopenias. We identified common patterns in complication management, but also significant variety in clinical management of the centers in important aspects. Our results demonstrate a high medical need for treatment harmonization and future clinical research in the following areas: treatment of steroid-refractory and very severe cytokine release syndrome/neurotoxicity, treatment of cytopenia, early discharge and outpatient management, as well as immunoglobulin substitution.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3557-3565"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal evolution from B-cell acute lymphoblastic leukemia with <I>BCR::ABL1</I> multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.","authors":"Mei-Jing Liu, Lan Dai, Li Yao, Kai-Wen Tan, Han-Yu Cao, Si-Man Huang, Chao-Ling Wan, Yuan-Hong Huang, Yang Zhang, Wen-Jie Gong, Sheng-Li Xue","doi":"10.3324/haematol.2024.285574","DOIUrl":"10.3324/haematol.2024.285574","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3821-3825"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes and genetic dynamics of acute myeloid leukemia at first relapse.","authors":"Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D DiNardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi","doi":"10.3324/haematol.2024.285057","DOIUrl":"10.3324/haematol.2024.285057","url":null,"abstract":"<p><p>Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended to disappear, whereas clonal hematopoiesis-related mutations or TP53 tended to persist. Patients with normal karyotypes tended to acquire cytogenetic abnormalities at relapse. Patients treated intensively had a higher rate of emergence of TP53 mutations (16%), compared to patients given low-intensity treatment (1%, P=0.009). The overall response rates were 38% and 35% for patients treated with salvage intensive treatment or low-intensity treatment, respectively. Seventeen patients (10%) underwent allogeneic stem cell transplantation after salvage therapy. The median overall survival duration after relapse was 5.3 months, with a 1-year overall survival rate of 17.6%. Complex karyotype (hazard ratio [HR]=2.14, P<0.001), a KMT2A rearrangement (HR=3.52, P=0.011), time in remission <12 months (HR=1.71, P=0.011), and an elevated white blood cell count at relapse (HR=2.38, P=0.005) were independent risk factors for overall survival duration. More effective frontline and maintenance therapies are warranted to prevent relapsed AML.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3543-3556"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of 'multi-hit' <i>versus</i> 'single-hit' <i>TP53</i> alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases.","authors":"Talha Badar, Ahmad Nanaa, Ehab Atallah, Rory M Shallis, Emily C Craver, Zhuo Li, Aaron D Goldberg, Antoine N Saliba, Anand Patel, Jan P Bewersdorf, Adam Duvall, Madelyn Burkart, Danielle Bradshaw, Yasmin Abaza, Maximilian Stahl, Neil Palmisiano, Guru Subramanian Guru Murthy, Amer M Zeidan, Vamsi Kota, Mrinal M Patnaik, Mark R Litzow","doi":"10.3324/haematol.2024.285000","DOIUrl":"10.3324/haematol.2024.285000","url":null,"abstract":"<p><p>While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation (TP53MT) compared to a single-hit (SH) mutation in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an in-depth analysis utilizing data from ten US academic institutions to study differences in molecular characteristics and outcomes of SH (N=139) versus MH (N=243) TP53MT AML. Complex cytogenetics were more common in MH than in SH TP53MT AML (P<0.001); whereas ASXL1 (P<0.001), RAS (P<0.001), splicing factor (P=0.003), IDH1/2 (P=0.001), FLT3 ITD (P<0.001) and NPM1 (P=0.005) mutations clustered significantly with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between patients with SH or MH disease (event-free survival: 3.0 vs. 2.20 months, respectively, P=0.22; overall survival: 8.50 vs. 7.53 months, respectively, P=0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate were associated with superior event-free survival (hazard ratio [HR]=0.44, 95% confidence interval [95% CI]: 0.19-1.01, P=0.05 and HR=0.34, 95% CI: 0.18-0.62, P<0.001) and overall survival (HR=0.24, 95% CI: 0.08-0.71, P=0.01 and HR=0.28, 95% CI: 0.16-0.47, P<0.001). Complex cytogenetics (HR=1.56, 95% CI: 1.01-2.40, P=0.04) retained an unfavorable significance for overall survival. Our analysis suggests that MH TP53MT is less relevant in independently predicting outcomes in patients with AML than in those with MDS.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3533-3542"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple myeloma in the young: insights on prognosis, clinical features and treatment outcome derived from nationwide German registry data and a nested multicenter sample.","authors":"Abdulaziz Kamili, Paymon Ahmadi, Lisa Leypoldt, Franziska Marquard, Christoph Schaefers, Ricardo Kosch, Frederik Peters, Henrik Kusche, Tanja Zamrik, Christine Hanoun, Maximilian Seib, Evgenii Shumilov, Theo Leitner, Cyrus Khandanpour, Carsten Bokemeyer, Katja Weisel, Susanne Ghandili","doi":"10.3324/haematol.2024.285630","DOIUrl":"10.3324/haematol.2024.285630","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3795-3799"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}