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However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)\u2010associated immature plasma cell phenotype, and particularly in those expressing B\u2013cell\u2010associated genes such as <jats:italic>PAX5<\/jats:italic> and <jats:italic>CD79A<\/jats:italic>. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD38 expression may be associated with the differentiation and maturation stages of myeloma cells. Furthermore, the <jats:italic>BCL2<\/jats:italic>\/<jats:italic>BCL2L1<\/jats:italic> ratio, a response marker of the BCL2 inhibitor venetoclax, was significantly higher in patients with the immature phenotype expressing B\u2013cell\u2010associated genes. The <jats:italic>BCL2<\/jats:italic>\/<jats:italic>BCL2L1<\/jats:italic> ratio and CD38 expression were significantly negatively correlated. We also confirmed that patients with translocation t(11;14) expressing B\u2013cell\u2010associated genes were indeed less sensitive to daratumumab\u2010mediated direct cytotoxicity but highly sensitive to venetoclax treatment in ex vivo assays. Moreover, all\u2010<jats:italic>trans<\/jats:italic>\u2010retinoic acid, which enhances CD38 expression and induces cell differentiation in myeloma cells, reduced B\u2010cell marker expression and the <jats:italic>BCL2<\/jats:italic>\/<jats:italic>BCL2L1<\/jats:italic> ratio in myeloma cell lines, leading to reduced efficacy of venetoclax. Venetoclax specifically induces cell death in myeloma with t(11;14), although why patients with translocation t(11;14) show BCL2 dependence is unclear. These results suggest that BCL2 dependence, as well as CD38 expression, are deeply associated with the differentiation and maturation stages of myeloma cells. This study highlights the importance of examining t(11;14) and considering cell maturity in myeloma treatment strategies.<\/jats:p>","DOI":"10.1111\/cas.15073","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T08:36:15Z","timestamp":1626770175000},"page":"3645-3654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Multiple myeloma with t(11;14)\u2010associated immature phenotype has lower CD38 expression and higher BCL2 dependence"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-2446","authenticated-orcid":false,"given":"Akihiro","family":"Kitadate","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology Department of Medicine Kameda Medical Center Kamogawa Japan"},{"name":"Department of Hematology, Nephrology, and Rheumatology Akita University Graduate School of Medicine Akita 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