Live kinase B1 maintains CD34+CD38- AML cell proliferation and self-renewal

Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34(+)CD38(-) fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34(+)CD38(-) AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34(+)CD38(-) AML cells, induced CD34(+)CD38(-) AML cells into G2/M phase, and enhanced the sensitivity of CD34(+)CD38(-) AML cells to chemotherapy. Furthermore, LKB1 downregulation in CD34(+)CD38(-) AML cells inhibited tumor formation in NOD-SCID mice. Downregulation of LKB1 gene makes LSCs partly loose the characters as stem cells. Gene expression microarray showed that MAPK/ERK pathway was implicated in the regulation of CD34(+)CD38(-) AML cell proliferation by LKB1. Together, these findings demonstrate that LKB1 plays an important role in the maintenance of LSCs, which may be responsible for drug resistance and AML relapse.