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.
KeywordsLive kinase B1 Acute myeloid leukemia Leukemia stem cells
Huihan Wang acknowledges grant support from the National Natural Science Foundation of China (81100376). Aijun Liao acknowledges grant support from the National Natural Science Foundation of China (81272629).
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