Acute myeloid leukemia (AML), an aggressive cancer of the blood and bone marrow, is a relatively rare cancer. But it usually gets worse quickly if left untreated. The five-year survival rate for AML patients is only 26%. In America, AML accounts for roughly 1% of all cancer death. In Great Britain, there were around 3,100 cases of AML in 2014, and AML incidence rates have increased by 7% over the past ten years. Recently, researchers from Leibniz Institute for Experimental Virology (LIEV), Engelhardt Institute for Molecular Biology, Johann Wolfgang Goethe-University and Link?ping University have revealed that a protein believed to be a tumor suppressor actually contributes to the development of AML. It is well known that cell proliferation and differentiation is regulated by elaborate gene regulatory networks. Deregulation of the networks is a key step during carcinogenesis. AML is caused by the cooperative action of different genetic and epigenetic alterations. Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene represent one of the most frequent classes of AML mutations. Patients harboring FLT3 mutation tend to have a poor prognosis. Prior studies have shown that AML patients with FLT3 mutation have high levels of a protein called Runt-related transcription factor 1 (RUNX1). RUNX1 is a transcription factor that helps control the development of blood cells, and it is believed to have tumor suppressor effect. Why do these AML patients have increased levels of a tumor suppressor? Some hypothesize that high levels of RUNX1 may contribute to AML development. To test this hypothesis, LIEV researchers collaborated with other institutes to study the effects of both RUNX1 and mutation in FLT3. Results showed that FLT3 mutation directly influences the activity of RUNX1, and then up-regulated RUNX1 cooperates with mutant FLT3 to induce AML. Furthermore, inactivating RUNX1 reduces the ability of human AML cells expressing mutant FLT3 to form tumors in experimental mice, suggesting that RUNX1 is critical for FLT3-induced AML. So blocking RUNX1 activity may enhance the efficacy of treatment strategies using FLT3 inhibitors. Like other transcription factors, the RUNX1 protein binds to specific regions of DNA and helps control the activity of particular genes. The researchers also found that?Hhex?is a direct target of RUNX1 and FLT3 mutation stimulation, and discovered high?HHEX?expression in FLT3-mutation AMLs. In addition, HHEX may also cooperate with FLT3 mutation to induce AML. Collectively, the study elucidates the oncogenic function of RUNX1 in AML. Cusabio produces FLT3, RUNX1 and Recombinant DRD2.
