{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:06:13Z","timestamp":1790885173803,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Education, Culture, Sports and Technology of Japan","award":["25K11678"],"award-info":[{"award-number":["25K11678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell dyscrasia. According to revised diagnostic criteria, pPCL is defined by the presence of \u22655% circulating plasma cells (CPCs) in the peripheral blood of patients with newly diagnosed multiple myeloma (NDMM). pPCL is characterized by a distinct cytogenetic profile, including frequent t(11;14), MAF\/MAB translocations, 1q gain, and del(17p). While t(11;14) is generally associated with a favorable prognosis, the coexistence of multiple high-risk cytogenetic abnormalities is linked to poorer outcomes. Tandem autologous hematopoietic stem cell transplantation and novel anti-myeloma agents have improved survival in some patients; however, overall prognosis remains poor, particularly in those ineligible for transplantation. Venetoclax and emerging immunotherapies, such as CAR-T cells and bispecific antibodies, show promise and merit clinical trials focused on pPCL-enriched cohorts. Additionally, recent findings associating even minimal CPCs with adverse outcomes in NDMM support broader inclusion criteria in future trials. A deeper understanding of pPCL\u2019s molecular pathology is critical for the development of effective targeted therapies. This article reviews recent advances in the molecular understanding of and treatment strategies for pPCL.<\/jats:p>","DOI":"10.3390\/ijms26136166","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T03:33:25Z","timestamp":1750995205000},"page":"6166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Primary Plasma Cell Leukemia: Recent Advances in Molecular Understanding and Treatment Approaches"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6681-8927","authenticated-orcid":false,"given":"Ichiro","family":"Hanamura","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2165-7565","authenticated-orcid":false,"given":"Sivasundaram","family":"Karnan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-2921","authenticated-orcid":false,"given":"Akinobu","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Food and Nutritional Environment, College of Human Life and Environment, Kinjo Gakuin University, Nagoya 463-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9976","authenticated-orcid":false,"given":"Akiyoshi","family":"Takami","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/archinte.133.5.813","article-title":"Plasma cell leukemia. 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