ABSTRACT
Resistance to chemotherapy remains a major obstacle in the treatment of acute myeloid leukemia (AML) and novel treatment strategies are warranted. FLT3 plays a significant role in hematopoiesis and a pathogenic role in the onset, development, and progression of AML. Chromosomal translocations associated with AML typically involve transcription regulators, which after recombination give rise to functional hybrid genes that encode for fusion proteins with abnormal function. AML is the consequence of cooperation between class I and class II mutations, resulting in proliferative and survival advantages of hematopoietic cells and impaired differentiation. Class I mutations include activating point mutations in receptor tyrosine kinases expressed in early myeloid progenitors, such as FLT3 and c-KIT. The phosphorylation status of proteins is balanced by the action of protein tyrosine kinases and protein tyrosine phosphatases. The hydrolysis of phosphoester bonds on tyrosine residues of proteins differs from threonine and serine in that it is metal-ion independent.
