Targeting integrin linked kinase and FMS-like tyrosine kinase-3 is cytotoxic to acute myeloid leukemia stem cells but spares normal progenitors.

摘要

Acute myeloid leukemia (AML) is maintained by rare leukemia-initiating cells (L-ICs). FLT3 and/or PI3K pathways are often dysregulated in AML and may be important for L-IC survival. The presence of PI3K pathway intermediate integrin linked kinase (ILK), and FLT3 was confirmed in five L-IC-enriched AML patient samples. Treatment of AML cells with QLT0267, an inhibitor of ILK and FLT3, decreased survival of long-term suspension culture-initiating cells and NOD/SCID mouse L-IC. In contrast, little toxicity toward normal bone marrow progenitors was observed, demonstrating that candidate leukemic stem cells can be eliminated by inhibition of these targets while normal hematopoietic counterparts are spared.