Blood Cancer Discovery最新文献

{"title":"Highlighted research articles","authors":"","doi":"10.1158/2643-3230.bcd-4-5-iti","DOIUrl":"https://doi.org/10.1158/2643-3230.bcd-4-5-iti","url":null,"abstract":"In This Issue| September 01 2023 Highlighted research articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2023 American Association for Cancer Research2023American Association for Cancer Research Blood Cancer Discov (2023) 4 (5): 337. https://doi.org/10.1158/2643-3230.BCD-4-5-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record September 1 2023 Citation Highlighted research articles. Blood Cancer Discov 1 September 2023; 4 (5): 337. https://doi.org/10.1158/2643-3230.BCD-4-5-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Biomarkers predicting CAR T-cell (CAR T) therapy outcomes in myeloma remain to be established. In this prespecified analysis of the KarMMa trial, Paiva et al. show that persistent measurable residual disease (MRD) around the time of peak expansion correlates with primary resistance to idecabtagene vicleucel. Associations of outcomes with M-protein and circulating plasma cells over the 1-year course were distinct from their profiles following traditional myeloma treatments, highlighting the unique biological mechanism of CAR T therapy. The findings offer one of the first clinical guides to using biomarkers for tailoring salvage therapy following CAR T in myeloma. See article, p. 365. The hallmarks of cancer include deregulated cellular metabolism and epigenetic reprogramming. In this work, Toyoda et al. show that a viral oncogene encoded in human T-cell leukemia virus type 1 (HTLV-1), HTLV-1 bZIP factor (HBZ), upregulates TAp73 by its two molecular forms, HBZ RNA and HBZ protein, via... You do not currently have access to this content.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136354969","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":"MRD and Plasma Cell Dynamics after CAR T-cell Therapy in Myeloma.","authors":"Ola Landgren, Dickran Kazandjian","doi":"10.1158/2643-3230.BCD-23-0134","DOIUrl":"10.1158/2643-3230.BCD-23-0134","url":null,"abstract":"<p><strong>Summary: </strong>In this issue, Paiva and colleagues characterize the dynamics of minimal residual disease (MRD) and clinical responses during chimeric antigen receptor (CAR) T-cell therapy of relapsed/refractory multiple myeloma. Although both correlate with prolonged progression-free survival, MRD is reached faster in the bone marrow than complete response in peripheral blood; consequently, the study addresses the need for future guidelines to explore new MRD-negative definitions that are independent of the monoclonal (M) protein to overcome this limitation, particularly in clinical trials using early depth of response as an endpoint. See related article by Paiva et al., p. 365 (1).</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"346-348"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"17th International Conference on Malignant Lymphoma: Key Takeaways.","authors":"","doi":"10.1158/2643-3230.BCD-ND2023-0003","DOIUrl":"10.1158/2643-3230.BCD-ND2023-0003","url":null,"abstract":"<p><p>The 17th International Conference on Malignant Lymphoma (ICML) took place in Lugano, Switzerland, from June 13-17 this year. The conference has been held every 2 to 3 years since its inception in 1981 and has become a significant and influential gathering for lymphoma researchers from around the world, this year hosting 4,761 registered attendees. Here, we provide some highlights of what we felt were the most noteworthy findings, both clinical and pre-clinical, across various lymphoma entities, presented at the 17th ICML.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"342-345"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Q&A: Riccardo Dalla-Favera on Cancer Genetics.","authors":"","doi":"10.1158/2643-3230.BCD-ND2023-0001","DOIUrl":"10.1158/2643-3230.BCD-ND2023-0001","url":null,"abstract":"","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"339-341"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML.","authors":"Lanpeng Chen, Eline Pronk, Claire van Dijk, Yujie Bian, Jacqueline Feyen, Tim van Tienhoven, Meltem Yildirim, Paola Pisterzi, Madelon M E de Jong, Alejandro Bastidas, Remco M Hoogenboezem, Chiel Wevers, Eric M Bindels, Bob Löwenberg, Tom Cupedo, Mathijs A Sanders, Marc H G P Raaijmakers","doi":"10.1158/2643-3230.BCD-23-0043","DOIUrl":"10.1158/2643-3230.BCD-23-0043","url":null,"abstract":"<p><p>Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR+ stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors are predicted to repress high-output hematopoietic stem cell subsets in NPM1-mutated acute myeloid leukemia (AML), with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcomes after chemotherapy across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment.</p><p><strong>Significance: </strong>Tumor-promoting inflammation is considered an enabling characteristic of tumorigenesis, but mechanisms remain incompletely understood. By deciphering the predicted signaling between tissue-resident stem cells and their neoplastic counterparts with their environment, we identify inflammatory remodeling of stromal niches as a determinant of normal tissue repression and clinical outcomes in human AML. See related commentary by Lisi-Vega and Méndez-Ferrer, p. 349. This article is featured in Selected Articles from This Issue, p. 337.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"394-417"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion.","authors":"Kosuke Toyoda, Jun-Ichirou Yasunaga, Takafumi Shichijo, Yuichiro Arima, Kenichi Tsujita, Azusa Tanaka, Tarig Salah, Wenyi Zhang, Osama Hussein, Miyu Sonoda, Miho Watanabe, Daisuke Kurita, Kazutaka Nakashima, Kyohei Yamada, Hiroaki Miyoshi, Koichi Ohshima, Masao Matsuoka","doi":"10.1158/2643-3230.BCD-22-0139","DOIUrl":"10.1158/2643-3230.BCD-22-0139","url":null,"abstract":"<p><p>Acceleration of glycolysis is a common trait of cancer. A key metabolite, lactate, is typically secreted from cancer cells because its accumulation is toxic. Here, we report that a viral oncogene, HTLV-1 bZIP factor (HBZ), bimodally upregulates TAp73 to promote lactate excretion from adult T-cell leukemia-lymphoma (ATL) cells. HBZ protein binds to EZH2 and reduces its occupancy of the TAp73 promoter. Meanwhile, HBZ RNA activates TAp73 transcription via the BATF3-IRF4 machinery. TAp73 upregulates the lactate transporters MCT1 and MCT4. Inactivation of TAp73 leads to intracellular accumulation of lactate, inducing cell death in ATL cells. Furthermore, TAp73 knockout diminishes the development of inflammation in HBZ-transgenic mice. An MCT1/4 inhibitor, syrosingopine, decreases the growth of ATL cells in vitro and in vivo. MCT1/4 expression is positively correlated with TAp73 in many cancers, and MCT1/4 upregulation is associated with dismal prognosis. Activation of the TAp73-MCT1/4 pathway could be a common mechanism contributing to cancer metabolism.</p><p><strong>Significance: </strong>An antisense gene encoded in HTLV-1, HBZ, reprograms lactate metabolism and epigenetic modification by inducing TAp73 in virus-positive leukemic cells. A positive correlation between TAp73 and its target genes is also observed in many other cancer cells, suggesting that this is a common mechanism for cellular oncogenesis. This article is featured in Selected Articles from This Issue, p. 337.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"374-393"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Inflamed Niche: A Double-Edged Sword in AML?","authors":"Livia E Lisi-Vega, Simón Méndez-Ferrer","doi":"10.1158/2643-3230.BCD-23-0125","DOIUrl":"10.1158/2643-3230.BCD-23-0125","url":null,"abstract":"<p><strong>Summary: </strong>Although inflammation has long been recognized as a hallmark of many cancers, including acute myeloid leukemia (AML), how it affects individual cells of the tumor microenvironment and their interaction with normal and neoplastic cells is incompletely understood. A comprehensive single-cell transcriptomic analysis of human bone marrow from patients with AML and healthy individuals identified skewing of stem cell and stromal cell populations in AML toward proinflammatory states associated with reduced risk of relapse, paralleling previous findings in mouse models and suggesting that inflamed bone marrow mesenchymal stromal cells might be a double-edged sword in AML by hampering normal hematopoiesis (while AML cells appear comparatively more resilient) but also rendering AML cells more susceptible to chemotherapy or immune attack. See related article by Chen et al., p. 394 (7) .</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"349-351"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10170673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase Ib/II Study of Ivosidenib with Venetoclax ± Azacitidine in IDH1-Mutated Myeloid Malignancies.","authors":"Curtis A Lachowiez, Sanam Loghavi, Zhihong Zeng, Tomoyuki Tanaka, Yi June Kim, Hidetaka Uryu, Sven Turkalj, Niels Asger Jakobsen, Marlise R Luskin, Dzifa Y Duose, Rebecca S S Tidwell, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Lucia Masarova, George D Tippett, Prithviraj Bose, Elias J Jabbour, Farhad Ravandi, Naval G Daver, Guillermo Garcia-Manero, Hagop Kantarjian, Jacqueline S Garcia, Paresh Vyas, Koichi Takahashi, Marina Konopleva, Courtney D DiNardo","doi":"10.1158/2643-3230.BCD-22-0205","DOIUrl":"10.1158/2643-3230.BCD-22-0205","url":null,"abstract":"<p><p>The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD--negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving ≥5 treatment cycles (N = 14). Median event-free survival and overall survival were 36 [94% CI, 23-not reached (NR)] and 42 (95% CI, 42-NR) months. Patients with signaling gene mutations appeared to particularly benefit from the triplet regimen. Longitudinal single-cell proteogenomic analyses linked cooccurring mutations, antiapoptotic protein expression, and cell maturation to therapeutic sensitivity of IDH1-mutated clones. No IDH isoform switching or second-site IDH1 mutations were observed, indicating combination therapy may overcome established resistance pathways to single-agent IVO.</p><p><strong>Significance: </strong>IVO + VEN + AZA is safe and active in patients with IDH1-mutated myeloid malignancies. Combination therapy appears to overcome resistance mechanisms observed with single-agent IDH-inhibitor use, with high MRD-negative remission rates. Single-cell DNA ± protein and time-of-flight mass-cytometry analysis revealed complex resistance mechanisms at relapse, highlighting key pathways for future therapeutic intervention. This article is highlighted in the In This Issue feature, p. 247.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 4","pages":"276-293"},"PeriodicalIF":11.2,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9782093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia.","authors":"Andriana G Kotini, Saul Carcamo, Nataly Cruz-Rodriguez, Malgorzata Olszewska, Tiansu Wang, Deniz Demircioglu, Chan-Jung Chang, Elsa Bernard, Mark P Chao, Ravindra Majeti, Hanzhi Luo, Michael G Kharas, Dan Hasson, Eirini P Papapetrou","doi":"10.1158/2643-3230.BCD-22-0167","DOIUrl":"10.1158/2643-3230.BCD-22-0167","url":null,"abstract":"<p><p>The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.</p><p><strong>Significance: </strong>We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation. See related commentary by Doulatov, p. 252. This article is highlighted in the In This Issue feature, p. 247.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 4","pages":"318-335"},"PeriodicalIF":11.5,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC Models of Leukemia Come of Age.","authors":"Sergei Doulatov","doi":"10.1158/2643-3230.BCD-23-0041","DOIUrl":"10.1158/2643-3230.BCD-23-0041","url":null,"abstract":"<p><strong>Summary: </strong>In this issue of Blood Cancer Discovery, Kotini and colleagues present a strategy for large-scale reprogramming of primary human acute myeloid leukemias (AML) to induced pluripotent stem cell (iPSC). They show that the hematopoietic differentiation of AML iPSCs gives rise to transplantable leukemias with remarkable molecular similarity to the original patients' AML, providing new models and insights into the disease. See related article by Kotini et al., p. 318 (7) .</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 4","pages":"252-253"},"PeriodicalIF":11.2,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9793437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}