Blood Cancer Discovery最新文献

{"title":"AACR Cancer Centers Alliance: Fostering Collaboration and Innovation to Advance Lifesaving Scientific Discoveries for Patients.","authors":"Carlos L Arteaga, John L Cleveland, Margaret Foti, Ruben A Mesa, Louis M Weiner, Cheryl L Willman, David A Tuveson","doi":"10.1158/2643-3230.BCD-23-0187","DOIUrl":"10.1158/2643-3230.BCD-23-0187","url":null,"abstract":"<p><strong>Summary: </strong>Basic and clinical cancer research discoveries stemming from the nation's cancer centers have markedly improved outcomes for many cancer patients. Despite this forward momentum in our progress against this complex disease, cancer in all its forms remains a major public health challenge that touches the lives of nearly every American, either directly or indirectly. The newly formed AACR Cancer Centers Alliance will accelerate the pace of discovery by providing an ongoing mechanism for transferring new knowledge, sharing resources, developing national demonstration projects, and driving innovation that impacts cancer science, cancer care delivery, and science and health policy.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"420-422"},"PeriodicalIF":11.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142208","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":"Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel.","authors":"Bruno Paiva, Irene Manrique, Julie Rytlewski, Timothy Campbell, Christian C Kazanecki, Nathan Martin, Larry D Anderson, Jesús G Berdeja, Sagar Lonial, Noopur S Raje, Yi Lin, Philippe Moreau, Jesús F San-Miguel, Nikhil C Munshi, Shari M Kaiser","doi":"10.1158/2643-3230.BCD-23-0044","DOIUrl":"10.1158/2643-3230.BCD-23-0044","url":null,"abstract":"<p><p>The role of measurable residual disease (MRD) in multiple myeloma patients treated with chimeric antigen receptor (CAR) T cells is uncertain. We analyzed MRD kinetics during the first year after idecabtagene vicleucel (ide-cel) infusion in 125 relapsed/refractory multiple myeloma patients enrolled in KarMMa. At month 1 after ide-cel, there were no differences in progression-free survival (PFS) between patients in less than complete response (CR) versus those in CR; only MRD status was predictive of significantly different PFS at this landmark. In patients with undetectable MRD at 3 months and beyond, PFS was longer in those achieving CR versus <CR. Persistent MRD in the 10-6 logarithmic range and reappearance of normal plasma cells in MRD-negative patients were associated with inferior PFS. This study unveils different prognostic implications of serological and MRD response dynamics after ide-cel and suggests the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T-cell functionality.</p><p><strong>Significance: </strong>This is one of the first studies evaluating the impact of CR and MRD dynamics after CAR T therapy in relapsed/refractory multiple myeloma. These data help interpret the prognostic significance of serological and MRD responses at early and late time points after CAR T-cell infusion. See related commentary by Landgren and Kazandjian, p. 346 . This article is featured in Selected Articles from This Issue, p. 337.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"365-373"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144118","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":"Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches.","authors":"Pramod C Nair, Jacob Piehler, Denis Tvorogov, David M Ross, Angel F Lopez, Jason Gotlib, Daniel Thomas","doi":"10.1158/2643-3230.BCD-22-0189","DOIUrl":"10.1158/2643-3230.BCD-22-0189","url":null,"abstract":"<p><p>Selective inhibitors of Janus kinase (JAK) 2 have been in demand since the discovery of the JAK2 V617F mutation present in patients with myeloproliferative neoplasms (MPN); however, the structural basis of V617F oncogenicity has only recently been elucidated. New structural studies reveal a role for other JAK2 domains, beyond the kinase domain, that contribute to pathogenic signaling. Here we evaluate the structure-based approaches that led to recently-approved type I JAK2 inhibitors (fedratinib and pacritinib), as well as type II (BBT594 and CHZ868) and pseudokinase inhibitors under development (JNJ7706621). With full-length JAK homodimeric structures now available, superior selective and mutation-specific JAK2 inhibitors are foreseeable.</p><p><strong>Significance: </strong>The JAK inhibitors currently used for the treatment of MPNs are effective for symptom management but not for disease eradication, primarily because they are not strongly selective for the mutant clone. The rise of computational and structure-based drug discovery approaches together with the knowledge of full-length JAK dimer complexes provides a unique opportunity to develop better targeted therapies for a range of conditions driven by pathologic JAK2 signaling.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"352-364"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199401","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":"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}