Pub Date : 2024-10-11DOI: 10.1182/blood.2023023156
Nicola Gökbuget, Björn Steffen
Despite advancements in new treatments, management of older patients with acute lymphoblastic leukaemia (ALL) remains an unmet medical need. With increasing age, ALL patients have a significantly lower CR rate, higher early mortality and relapse rate, and poorer survival compared to younger patients. This is attributed to a higher prevalence of adverse prognostic factors among older individuals and reduced tolerance to chemotherapy. Progress has been made in tailoring moderately intensive chemotherapy protocols for Ph/BCR-ABL (Ph) negative ALL in older patients, and recent phase II studies have explored integrating immunotherapy into initial treatment with very promising results. However, establishing new standard regimens for this age group remains and improving general management strategy is a pending task.
{"title":"How I Treat Older Patients with Ph/BCR-ABL-Negative Acute Lymphoblastic Leukemia.","authors":"Nicola Gökbuget, Björn Steffen","doi":"10.1182/blood.2023023156","DOIUrl":"https://doi.org/10.1182/blood.2023023156","url":null,"abstract":"<p><p>Despite advancements in new treatments, management of older patients with acute lymphoblastic leukaemia (ALL) remains an unmet medical need. With increasing age, ALL patients have a significantly lower CR rate, higher early mortality and relapse rate, and poorer survival compared to younger patients. This is attributed to a higher prevalence of adverse prognostic factors among older individuals and reduced tolerance to chemotherapy. Progress has been made in tailoring moderately intensive chemotherapy protocols for Ph/BCR-ABL (Ph) negative ALL in older patients, and recent phase II studies have explored integrating immunotherapy into initial treatment with very promising results. However, establishing new standard regimens for this age group remains and improving general management strategy is a pending task.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406068","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}
Pub Date : 2024-10-11DOI: 10.1182/blood.2024025828
Jingqiong Hu, Cynthia E Dunbar
The United States Food and Drug Administration (FDA) announcement in November 2023 regarding reports of the occurrence of secondary T-cell lymphomas in patients receiving chimeric antigen receptor T-cells (CAR-T) for B-cell malignancies resulted in widespread concern among patients, clinicians and scientists. Little information relevant to assessing causality, most importantly whether CAR retroviral or lentiviral vector genomic insertions contribute to oncogenesis, was initially available. However, since that time several publications have provided clinical and molecular details on three cases showing clonal CAR vector insertions in tumor cells but without firm evidence these insertions played any role in oncogenic transformation. In addition, several other cases have been reported without vector detected in tumor cells. In addition, epidemiologic analyses as well as institutional long-term CAR-T recipient cohort studies provide important additional information suggesting the risk of T-cell lymphomas following CAR-T therapies is extremely low. This review will provide a summary of information available to date, as well as review relevant prior research suggesting a low susceptibility of mature T-cells to insertional oncogenesis and documenting the almost complete lack of T-cell transformation following natural HIV infection. Alternative factors that may predispose patients treated with CAR-T cells to secondary hematologic malignancies, including immune dysfunction and clonal hematopoiesis, are discussed and likely play a greater role than insertional mutagenesis in secondary malignancies post-CAR therapies.
美国食品和药物管理局(FDA)于 2023 年 11 月公布了关于接受嵌合抗原受体 T 细胞(CAR-T)治疗 B 细胞恶性肿瘤的患者出现继发性 T 细胞淋巴瘤的报告,引起了患者、临床医生和科学家的广泛关注。最初,与评估因果关系相关的信息很少,最重要的是 CAR 逆转录病毒或慢病毒载体基因组插入是否会导致肿瘤发生。不过,从那时起,一些出版物提供了三个病例的临床和分子细节,这些病例显示肿瘤细胞中有克隆性 CAR 载体插入,但没有确凿证据表明这些插入在致癌转化中起了任何作用。此外,还报道了其他几例肿瘤细胞中未检测到载体的病例。此外,流行病学分析以及机构长期 CAR-T 受体队列研究也提供了重要的补充信息,表明 CAR-T 疗法后发生 T 细胞淋巴瘤的风险极低。本综述将总结迄今为止的信息,并回顾之前的相关研究,这些研究表明成熟 T 细胞对插入性肿瘤发生的易感性很低,并记录了自然感染 HIV 后几乎完全没有 T 细胞转化的情况。报告还讨论了可能使接受 CAR-T 细胞治疗的患者易患继发性血液系统恶性肿瘤的其他因素,包括免疫功能障碍和克隆造血,这些因素在 CAR 疗法后继发性恶性肿瘤中的作用可能比插入突变更大。
{"title":"T-Cell Lymphomas in Recipients of CAR-T Cells: Assessing Risks and Causalities.","authors":"Jingqiong Hu, Cynthia E Dunbar","doi":"10.1182/blood.2024025828","DOIUrl":"https://doi.org/10.1182/blood.2024025828","url":null,"abstract":"<p><p>The United States Food and Drug Administration (FDA) announcement in November 2023 regarding reports of the occurrence of secondary T-cell lymphomas in patients receiving chimeric antigen receptor T-cells (CAR-T) for B-cell malignancies resulted in widespread concern among patients, clinicians and scientists. Little information relevant to assessing causality, most importantly whether CAR retroviral or lentiviral vector genomic insertions contribute to oncogenesis, was initially available. However, since that time several publications have provided clinical and molecular details on three cases showing clonal CAR vector insertions in tumor cells but without firm evidence these insertions played any role in oncogenic transformation. In addition, several other cases have been reported without vector detected in tumor cells. In addition, epidemiologic analyses as well as institutional long-term CAR-T recipient cohort studies provide important additional information suggesting the risk of T-cell lymphomas following CAR-T therapies is extremely low. This review will provide a summary of information available to date, as well as review relevant prior research suggesting a low susceptibility of mature T-cells to insertional oncogenesis and documenting the almost complete lack of T-cell transformation following natural HIV infection. Alternative factors that may predispose patients treated with CAR-T cells to secondary hematologic malignancies, including immune dysfunction and clonal hematopoiesis, are discussed and likely play a greater role than insertional mutagenesis in secondary malignancies post-CAR therapies.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406069","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024026379
Stefan K Alig
{"title":"FISHing for clarity in double-hit lymphomas.","authors":"Stefan K Alig","doi":"10.1182/blood.2024026379","DOIUrl":"10.1182/blood.2024026379","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399326","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2023023727
Elsa Bernard, Robert P Hasserjian, Peter L Greenberg, Juan E Arango Ossa, Maria Creignou, Heinz Tuechler, Jesus Gutierrez-Abril, Dylan Domenico, Juan S Medina-Martinez, Max Levine, Konstantinos Liosis, Noushin Farnoud, Maria Sirenko, Martin Jädersten, Ulrich Germing, Guillermo Sanz, Arjan A van de Loosdrecht, Yasuhito Nannya, Olivier Kosmider, Matilde Y Follo, Felicitas Thol, Lurdes Zamora, Ronald F Pinheiro, Andrea Pellagatti, Harold K Elias, Detlef Haase, Christina Ganster, Lionel Ades, Magnus Tobiasson, Laura Palomo, Matteo Giovanni Della Porta, Pierre Fenaux, Monika Belickova, Michael R Savona, Virginia M Klimek, Fabio P S Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Solé, Uwe Platzbecker, Michael Heuser, Peter Valent, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H Jansen, José Cervera, Norbert Gattermann, Benjamin L Ebert, Rafael Bejar, Luca Malcovati, Seishi Ogawa, Mario Cazzola, Eva Hellström-Lindberg, Elli Papaemmanuil
Abstract: Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. Although genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations, and copy-neutral loss of heterozygosity were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91%, 43%, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and loss of heterozygosity at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow (BM) blast percentage across groups ranged from 1.5% to 10%, and the median overall survival ranged from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of BM blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and might inform future classification schemas and translational therapeutic research.
{"title":"Molecular taxonomy of myelodysplastic syndromes and its clinical implications.","authors":"Elsa Bernard, Robert P Hasserjian, Peter L Greenberg, Juan E Arango Ossa, Maria Creignou, Heinz Tuechler, Jesus Gutierrez-Abril, Dylan Domenico, Juan S Medina-Martinez, Max Levine, Konstantinos Liosis, Noushin Farnoud, Maria Sirenko, Martin Jädersten, Ulrich Germing, Guillermo Sanz, Arjan A van de Loosdrecht, Yasuhito Nannya, Olivier Kosmider, Matilde Y Follo, Felicitas Thol, Lurdes Zamora, Ronald F Pinheiro, Andrea Pellagatti, Harold K Elias, Detlef Haase, Christina Ganster, Lionel Ades, Magnus Tobiasson, Laura Palomo, Matteo Giovanni Della Porta, Pierre Fenaux, Monika Belickova, Michael R Savona, Virginia M Klimek, Fabio P S Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Solé, Uwe Platzbecker, Michael Heuser, Peter Valent, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H Jansen, José Cervera, Norbert Gattermann, Benjamin L Ebert, Rafael Bejar, Luca Malcovati, Seishi Ogawa, Mario Cazzola, Eva Hellström-Lindberg, Elli Papaemmanuil","doi":"10.1182/blood.2023023727","DOIUrl":"10.1182/blood.2023023727","url":null,"abstract":"<p><strong>Abstract: </strong>Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. Although genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations, and copy-neutral loss of heterozygosity were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91%, 43%, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and loss of heterozygosity at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow (BM) blast percentage across groups ranged from 1.5% to 10%, and the median overall survival ranged from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of BM blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and might inform future classification schemas and translational therapeutic research.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490841","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024026075
Jin Y Chen
{"title":"Breaking T-cell tolerance in the immune system.","authors":"Jin Y Chen","doi":"10.1182/blood.2024026075","DOIUrl":"10.1182/blood.2024026075","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399324","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024025938
Daniel E Bauer
{"title":"Genetic medicine gestating for α-thalassemia.","authors":"Daniel E Bauer","doi":"10.1182/blood.2024025938","DOIUrl":"10.1182/blood.2024025938","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399328","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024024230
Flavia Dei Zotti, Annie Qiu, Vivette D D'Agati, Shwatina Jagnarine, Emmalene Kyritsis, Anabel Miller, Maria Tredicine, Daysha Fliginger, Elizabeth F Stone, Sandhya Panch, Krystalyn E Hudson
Abstract: Immune checkpoint inhibitors (ICPis) have revolutionized cancer immunotherapy but also can induce autoimmune hemolytic anemia (AIHA), a severe disease with high mortality. However, the cellular and molecular mechanism(s) of AIHA secondary to ICPi therapy (ICPi-AIHA) are unclear, other than being initiated through decreased checkpoint inhibition. Herein, we report ICPi-AIHA in a novel mouse model that shows similar characteristics of known human ICPi-AIHA (eg, autoantibodies, hemolysis, and increased mortality). During ICPi-AIHA, there is the simultaneous reduction of 2 regulatory T-cell populations (FoxP3+ and Tr1 [type 1 regulatory cells]) and an increase in inflammatory T helper cell 17 (TH17). Moreover, a novel CD39+CD73-FoxP3-CD25- CD4+ T-cell subset (ie, CD39 single positive [CD39SP]) emerges, and early increases in CD39SP predict AIHA development; CD39 is an ectonuclease that breaks down adenosine triphosphate (ATP). Additionally, we found that boosting ATPase activity by injecting recombinant apyrase mitigates AIHA development and significant CD39SP reductions, both suggesting a functional role for CD39 and demonstrating a novel therapeutic approach. Importantly, CD39SP are detectable in multiple mouse models developing AIHA and in patients with AIHA, demonstrating applicability to idiopathic and secondary AIHA. Highlighting broader autoimmunity relevance, ICPi-treated NZB mice experienced accelerated onset and severity of lupus, including AIHA. Moreover, ICPi treatment of healthy B6 animals led to detectable CD39SP and development of autoantibodies against multiple autoantigens including those on red blood cells and platelets. Together, our findings provide further insight into the cellular and molecular mechanisms of ICPi-AIHA, leading to novel diagnostic and therapeutic approaches with translational potential for use in humans being treated with ICPi.
{"title":"Mitigation of checkpoint inhibitor-induced autoimmune hemolytic anemia through modulation of purinergic signaling.","authors":"Flavia Dei Zotti, Annie Qiu, Vivette D D'Agati, Shwatina Jagnarine, Emmalene Kyritsis, Anabel Miller, Maria Tredicine, Daysha Fliginger, Elizabeth F Stone, Sandhya Panch, Krystalyn E Hudson","doi":"10.1182/blood.2024024230","DOIUrl":"10.1182/blood.2024024230","url":null,"abstract":"<p><strong>Abstract: </strong>Immune checkpoint inhibitors (ICPis) have revolutionized cancer immunotherapy but also can induce autoimmune hemolytic anemia (AIHA), a severe disease with high mortality. However, the cellular and molecular mechanism(s) of AIHA secondary to ICPi therapy (ICPi-AIHA) are unclear, other than being initiated through decreased checkpoint inhibition. Herein, we report ICPi-AIHA in a novel mouse model that shows similar characteristics of known human ICPi-AIHA (eg, autoantibodies, hemolysis, and increased mortality). During ICPi-AIHA, there is the simultaneous reduction of 2 regulatory T-cell populations (FoxP3+ and Tr1 [type 1 regulatory cells]) and an increase in inflammatory T helper cell 17 (TH17). Moreover, a novel CD39+CD73-FoxP3-CD25- CD4+ T-cell subset (ie, CD39 single positive [CD39SP]) emerges, and early increases in CD39SP predict AIHA development; CD39 is an ectonuclease that breaks down adenosine triphosphate (ATP). Additionally, we found that boosting ATPase activity by injecting recombinant apyrase mitigates AIHA development and significant CD39SP reductions, both suggesting a functional role for CD39 and demonstrating a novel therapeutic approach. Importantly, CD39SP are detectable in multiple mouse models developing AIHA and in patients with AIHA, demonstrating applicability to idiopathic and secondary AIHA. Highlighting broader autoimmunity relevance, ICPi-treated NZB mice experienced accelerated onset and severity of lupus, including AIHA. Moreover, ICPi treatment of healthy B6 animals led to detectable CD39SP and development of autoantibodies against multiple autoantigens including those on red blood cells and platelets. Together, our findings provide further insight into the cellular and molecular mechanisms of ICPi-AIHA, leading to novel diagnostic and therapeutic approaches with translational potential for use in humans being treated with ICPi.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892827","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024026818
This article has been retracted; please see Elsevier's Article Correction, Retraction and Removal Policy (Article withdrawal | Elsevier policy).This article has been retracted at the request of the Editors and authors.Within the paper, image issues were identified in Figures 1, 4, and 6. Images within these figures show duplication, modification, or unmarked splices.The authors state that these figures cannot be used to support the conclusions of the paper.Authors Tai, Fulciniti, Song, Li, Morrison, Chauhan, Tassone, Ghobrial, and Anderson approve the retraction. Authors Hideshima, Leiba, Rumizen, Burger, Podar, Richardson, and Munshi did not respond.
{"title":"Tai Y-T, Fulciniti M, Hideshima T, Song W, Leiba M, Li X-F, Rumizen M, Burger P, Morrison A, Podar K, Chauhan D, Tassone P, Richardson P, Munshi NC, Ghobrial IM, Anderson KC. Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis. Blood. 2007;110(5):1656-1663.","authors":"","doi":"10.1182/blood.2024026818","DOIUrl":"10.1182/blood.2024026818","url":null,"abstract":"<p><p>This article has been retracted; please see Elsevier's Article Correction, Retraction and Removal Policy (Article withdrawal | Elsevier policy).This article has been retracted at the request of the Editors and authors.Within the paper, image issues were identified in Figures 1, 4, and 6. Images within these figures show duplication, modification, or unmarked splices.The authors state that these figures cannot be used to support the conclusions of the paper.Authors Tai, Fulciniti, Song, Li, Morrison, Chauhan, Tassone, Ghobrial, and Anderson approve the retraction. Authors Hideshima, Leiba, Rumizen, Burger, Podar, Richardson, and Munshi did not respond.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131815","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024025676
Lachlin Vaughan, John E Pimanda
{"title":"Seeing MDS through the lens of genomics.","authors":"Lachlin Vaughan, John E Pimanda","doi":"10.1182/blood.2024025676","DOIUrl":"10.1182/blood.2024025676","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399329","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}
Pub Date : 2024-10-10DOI: 10.1182/blood.2024025603
Brett Collinge, Susana Ben-Neriah, Laura K Hilton, Waleed Alduaij, Tracy Tucker, Graham W Slack, Pedro Farinha, Jeffrey W Craig, Merrill Boyle, Barbara Meissner, Diego Villa, Alina S Gerrie, Laurie H Sehn, Kerry J Savage, Ryan D Morin, Andrew J Mungall, Christian Steidl, David W Scott
Abstract: Fluorescence in situ hybridization (FISH) using break-apart probes is recommended for identifying high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). Unbalanced MYC break-apart patterns, in which the red or green signal is lost, are commonly reported as an equivocal result by clinical laboratories. In a cohort of 297 HGBCL-DH-BCL2, 13% of tumors had unbalanced MYC break-apart patterns with loss of red (LR; 2%) or loss of green (LG; 11%) signal. To determine the significance of these patterns, MYC rearrangements were characterized by sequencing in 130 HGBCL-DH-BCL2, including 3 LR and 14 LG tumors. A MYC rearrangement was identified for 71% of tumors with LR or LG patterns, with the majority involving immunoglobulin loci or other recurrent MYC rearrangement partners. The architecture of these rearrangements consistently preserved the rearranged MYC allele, with the MYC gene predicted to be on the derivative chromosome containing the signal that is still present in nearly all cases. MYC protein expression, MYC messenger RNA expression, and the proportion of tumors expressing the dark-zone signature was not significantly different between balanced and unbalanced groups. These results support a recommendation that unbalanced MYC break-apart FISH patterns be reported as positive for MYC rearrangement in the context of diagnosing HGBCL-DH-BCL2.
{"title":"Unbalanced MYC break-apart FISH patterns indicate the presence of a MYC rearrangement in HGBCL-DH-BCL2.","authors":"Brett Collinge, Susana Ben-Neriah, Laura K Hilton, Waleed Alduaij, Tracy Tucker, Graham W Slack, Pedro Farinha, Jeffrey W Craig, Merrill Boyle, Barbara Meissner, Diego Villa, Alina S Gerrie, Laurie H Sehn, Kerry J Savage, Ryan D Morin, Andrew J Mungall, Christian Steidl, David W Scott","doi":"10.1182/blood.2024025603","DOIUrl":"10.1182/blood.2024025603","url":null,"abstract":"<p><strong>Abstract: </strong>Fluorescence in situ hybridization (FISH) using break-apart probes is recommended for identifying high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). Unbalanced MYC break-apart patterns, in which the red or green signal is lost, are commonly reported as an equivocal result by clinical laboratories. In a cohort of 297 HGBCL-DH-BCL2, 13% of tumors had unbalanced MYC break-apart patterns with loss of red (LR; 2%) or loss of green (LG; 11%) signal. To determine the significance of these patterns, MYC rearrangements were characterized by sequencing in 130 HGBCL-DH-BCL2, including 3 LR and 14 LG tumors. A MYC rearrangement was identified for 71% of tumors with LR or LG patterns, with the majority involving immunoglobulin loci or other recurrent MYC rearrangement partners. The architecture of these rearrangements consistently preserved the rearranged MYC allele, with the MYC gene predicted to be on the derivative chromosome containing the signal that is still present in nearly all cases. MYC protein expression, MYC messenger RNA expression, and the proportion of tumors expressing the dark-zone signature was not significantly different between balanced and unbalanced groups. These results support a recommendation that unbalanced MYC break-apart FISH patterns be reported as positive for MYC rearrangement in the context of diagnosing HGBCL-DH-BCL2.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970593","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}