Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Sci. 2010 Mar;101(3):631-8. doi: 10.1111/j.1349-7006.2009.01440.x. Epub 2009 Nov 16.
Stem cells of acute myeloid leukemia (AML) have been identified as immunodeficient mouse-repopulating cells with a Lin(-)CD34(+)38(-) phenotype similar to normal hematopoietic stem cells. To identify the leukemia-propagating stem cell fraction of Philadelphia chromosome-positive (Ph(+)) leukemia, we serially transplanted human leukemia cells from patients with chronic myeloid leukemia blast crisis (n = 3) or Ph(+) acute lymphoblastic leukemia (n = 3) into NOD/SCID/IL-2Rgammac(-/-) mice. Engrafted cells were almost identical to the original leukemia cells as to phenotypes, IGH rearrangements, and karyotypes. CD34(+)CD38(-)CD19(+), CD34(+)38(+)CD19(+), and CD34(-)CD38(+)CD19(+) fractions could self-renew and transfer the leukemia, whereas the CD34(-)CD38(+)CD19(+) fraction did not stably propagate in NOD/SCID mice. These findings suggest that leukemia-repopulating cells in transformed Ph(+) leukemia are included in a lineage-committed but multilayered fraction, and that CD34(+) leukemia cells potentially emerge from CD34(-) populations.
急性髓系白血病 (AML) 的干细胞被鉴定为免疫缺陷的小鼠再群体细胞，其 Lin(-)CD34(+)38(-)表型类似于正常造血干细胞。为了鉴定费城染色体阳性 (Ph(+)) 白血病的白血病增殖干细胞部分，我们将来自慢性髓系白血病急变期患者的人白血病细胞（n=3）或 Ph(+)急性淋巴细胞白血病患者的人白血病细胞（n=3）连续移植到 NOD/SCID/IL-2Rgammac(-/-) 小鼠中。植入的细胞在表型、IGH 重排和核型方面与原始白血病细胞几乎完全相同。CD34(+)CD38(-)CD19(+)、CD34(+)38(+)CD19(+)和 CD34(-)CD38(+)CD19(+) 部分可以自我更新并转移白血病，而 CD34(-)CD38(+)CD19(+) 部分在 NOD/SCID 小鼠中不能稳定地增殖。这些发现表明，转化的 Ph(+)白血病中的白血病再群体细胞包含在一个谱系定向但多层次的部分中，并且 CD34(+)白血病细胞可能从 CD34(-)群体中出现。
