Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD / SCID / IL-2Rc^?/? mice

摘要

( Cancer Sci 2010; 101: 631–638) 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-2Rγc ^?/? 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.