Molecular mechanisms and therapeutic approach of residual leukemia

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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.