Genetic loss of MSI2 leads to down-regulation of the FLT3 receptor in both AML and BC-CML cells and concomitant impairment of clonogenic growth potential.
Twenty-five of 26 patients who were planned for post allo-HCT therapy received it (10 with myeloid malignancies received 5-azacytidine, 5 with FLT-3 ITD acute myeloid leukemia received sorafenib, 4 with Philadelphia-positive acute lymphoblastic leukemia or chronic myelogenous leukemia in blast crisis received dasatinib, or dasatinib followed by imatinib, and 5 with acute lymphoblastic leukemia received intrathecal cytarabine).
Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia).