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

Abstract

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. © 2009 Japanese Cancer Association.