{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:06:22Z","timestamp":1790841982048,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T00:00:00Z","timestamp":1657411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Janssen R&amp;D","award":["864044"],"award-info":[{"award-number":["864044"]}]},{"name":"Janssen R&amp;D","award":["2015344"],"award-info":[{"award-number":["2015344"]}]},{"name":"Janssen R&amp;D","award":["CA06927"],"award-info":[{"award-number":["CA06927"]}]},{"DOI":"10.13039\/100006221","name":"U.S.\/Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["864044"],"award-info":[{"award-number":["864044"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006221","name":"U.S.\/Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2015344"],"award-info":[{"award-number":["2015344"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006221","name":"U.S.\/Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["CA06927"],"award-info":[{"award-number":["CA06927"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute Comprehensive Cancer Center Support","doi-asserted-by":"publisher","award":["864044"],"award-info":[{"award-number":["864044"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute Comprehensive Cancer Center Support","doi-asserted-by":"publisher","award":["2015344"],"award-info":[{"award-number":["2015344"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute Comprehensive Cancer Center Support","doi-asserted-by":"publisher","award":["CA06927"],"award-info":[{"award-number":["CA06927"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is an aggressive malignancy that requires rapid treatment with chemotherapies to reduce tumor burden. However, these chemotherapies can compromise lymphocyte function, thereby hindering normal anti-tumor immune responses and likely limiting the efficacy of subsequent immunotherapy. To better understand these negative impacts, we assessed the immunological effects of standard-of-care AML therapies on lymphocyte phenotype and function over time. When compared to healthy donors, untreated AML patients showed evidence of lymphocyte activation and exhaustion and had more prevalent CD57+NKG2C+ adaptive NK cells, which was independent of human cytomegalovirus (HCMV) status. HMA\/venetoclax treatment resulted in a greater fraction of T cells with effector memory phenotype, inhibited IFN-\u03b3 secretion by CD8+ T cells, upregulated perforin expression in NK cells, downregulated PD-1 and 2B4 expression on CD4+ T cells, and stimulated Treg proliferation and CTLA-4 expression. Additionally, we showed increased expression of perforin and CD39 and enhanced IFN-\u03b3 production by T cells from pre-treatment blood samples of venetoclax-resistant AML patients. Our results provide insight into the lymphocyte status in previously untreated AML patients and the effects of standard-of-care treatments on their biology and functions. We also found novel pre-treatment characteristics of T cells that could potentially predict venetoclax resistance.<\/jats:p>","DOI":"10.3390\/cancers14143352","type":"journal-article","created":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T21:19:28Z","timestamp":1657487968000},"page":"3352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lymphocyte Exhaustion in AML Patients and Impacts of HMA\/Venetoclax or Intensive Chemotherapy on Their Biology"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-3875","authenticated-orcid":false,"given":"Dmitry","family":"Zhigarev","sequence":"first","affiliation":[{"name":"Blood Cell Development and Function Program, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"},{"name":"Department of Immunology, Pirogov Russian National Research Medical University, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya","family":"Varshavsky","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplant and Cellular Therapies, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"Alexander W.","family":"MacFarlane","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathiba","family":"Jayaguru","sequence":"additional","affiliation":[{"name":"Oncology Translational Research, Janssen R&D, Spring House, PA 19477, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barreyro","sequence":"additional","affiliation":[{"name":"Oncology Translational Research, Janssen R&D, Spring House, PA 19477, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Khoreva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Pirogov Russian National Research Medical University, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essel","family":"Dulaimi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Nejati","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Drenberg","sequence":"additional","affiliation":[{"name":"Oncology Translational Research, Janssen R&D, Spring House, PA 19477, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4665-7326","authenticated-orcid":false,"given":"Kerry S.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603636","DOI":"10.3389\/fonc.2020.603636","article-title":"MRD tailored therapy in AML: What we have learned so far","volume":"10","author":"Ngai","year":"2021","journal-title":"Front. 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