Eguchi Mariko, Eguchi-Ishimae Minenori, Ishii Eiichi
Department of Pediatrics, Ehime University Graduate School of Medicine.
Rinsho Ketsueki. 2015 Oct;56(10):1871-81. doi: 10.11406/rinketsu.56.1871.
Leukemic stem cells (LSCs) were originally identified in acute myeloid leukemia (AML) cases by using xenograft models, as a distinct cell population that can initiate leukemia in immunodeficient mice. Since then, many efforts have been made to clarify the identities of LSCs and other cancer stem cells in various cancer types, to both understand their biology and determine the most suitable targets for anti-cancer therapies. LSCs were identified as existing in the immature CD34+CD38- leukemic population in most AML cases, and these cells were found to share some features with normal hematopoietic stem cells. On the other hand, recent studies have shown that in childhood acute lymphoblastic leukemia (ALL), LSCs exist among B-lineage-committed progenitors expressing CD19. In contrast to AML, in which LSCs generate leukemic cells in a hierarchical order with LSCs at the top, leukemia propagation in childhood ALL is better explained by a stochastic model. In B-precursor ALL, LSCs form via acquisition of additional genetic change(s) in CD19+ B-lineage progenitor cells with self-renewing capacity. These LSCs possess a growth advantage and the capacity to produce progeny with the same ability as the LSCs. Identification of genetic and cellular targets in leukemic transformation is necessary to develop improved anti-cancer therapies.
白血病干细胞(LSCs)最初是在急性髓系白血病(AML)病例中通过异种移植模型鉴定出来的,它是一种独特的细胞群体,能够在免疫缺陷小鼠中引发白血病。从那时起,人们做出了许多努力来阐明各种癌症类型中LSCs和其他癌症干细胞的身份,以便了解它们的生物学特性并确定最适合的抗癌治疗靶点。在大多数AML病例中,LSCs被鉴定存在于未成熟的CD34+CD38-白血病细胞群体中,并且发现这些细胞与正常造血干细胞具有一些共同特征。另一方面,最近的研究表明,在儿童急性淋巴细胞白血病(ALL)中,LSCs存在于表达CD19的B系定向祖细胞中。与AML不同,AML中LSCs以等级顺序产生白血病细胞,LSCs处于顶端,而儿童ALL中的白血病传播用随机模型能更好地解释。在B前体ALL中,LSCs通过在具有自我更新能力的CD19+B系祖细胞中获得额外的基因变化而形成。这些LSCs具有生长优势,并且能够产生与LSCs具有相同能力的子代。鉴定白血病转化中的基因和细胞靶点对于开发改进的抗癌治疗方法是必要的。