Principal Investigator: Prof. Jasmeen Merzaban

Poster Presenter: Amal Kamal Abdel-Aziz



Counteracting the resistance of FLT3-ITD AML to FLT3 inhibitors




Abstract: In acute myeloid leukemia (AML), two main types of FLT3 mutations occur: i) FLT3 internal tandem duplication (FLT3-ITD) mutations and ii) FLT3-TKD mutations. Both types of FLT3 mutations promote constitutive (or ligand-independent) activation of FLT3 and thereby foster the proliferation and survival of AML.  FLT3-ITD mutations account for∼ 30–35% of the mutations in AML patients and are associated with poor prognosis. Tremendous efforts have been invested in developing FLT3 inhibitors. Despite the initial clinical efficacy of FLT3 inhibitors, many treated AML patients with mutated FLT3 eventually relapse.  To propel this field forward, interdisciplinary collaborations between researchers, medical oncologists and pharmaceutical experts are urged in multiple fronts to refine the use of FLT3-targeted therapeutic arsenal and conceive novel therapeutic approaches for treating patients with FLT3- mutated AML. Indeed, we are pursuing basic and translational studies to systematically investigate the molecular basis underlying the resistance of FLT3-ITD+ AMLs to FLT3 inhibitors and devise tolerable and efficacious therapeutic strategies to restore the antileukemic activity of FLT3 inhibitors.