Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic
acid represents the most successful pharmacological therapy of acute myeloid leukemia
(AML). Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin
(mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting
differentiation and blocking proliferation of AML. Most of these drugs are already in use
for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and
5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic.
Although most of these pharmacological modulators have been widely used for
decades, their mechanism of action is only partially understood. In this review, we summarize
the role of AMPK and mTOR in hematological malignancies and discuss the possible
role of pharmacological modulators in proliferation and differentiation of leukemia
Keywords: AML, AMPK, mTOR, rapamycin, metformin, AICAR, differentiation.
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