Molecular mechanisms and therapeutic approach of residual leukemia

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，我们将来自慢性髓性白血病急变或Ph+急性淋巴细胞白血病患者的人白血病细胞连续移植到NOD/SCID/IL-2 Rc γ^<null>小鼠中。移植的细胞几乎与原始白血病细胞相同。CD 34 + CD 38 + CD 19+、CD 34 + CD 38+ CD 19+和CD 34-CD 38 + CD 19+组分在NOD/SCID小鼠体内能自我更新并转移白血病细胞，而CD 34-CD 38 + CD 19+组分在NOD/SCID小鼠体内不能稳定增殖。这些研究结果表明，白血病再生细胞转化Ph+白血病包括在一个谱系承诺，但多层的部分，和CD 34+白血病细胞可能出现从CD 34-人口。

To identify the leukemia-propagating stem cell fraction of Philadelphia chro-mosome-positive (Ph+) leukemia, we serially transplanted human leukemia cells from patients with chronic myeloid leukemia blast crisis or Ph+ acute lymphoblastic leukemia into NOD/SCID/IL-2Rcγ^<null> mice. Engrafted cells were almost identical to the original leukemia cells. 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.