(Left) Signaling pathway of FLT3-WT (Right) Signaling pathway of FLT3-ITD1. Studies have shown that FLT3-ITD transformed cells injected into mice result in a leukemia-like syndrome. These FLT3-ITD transformed cells include Ba/F3 or 32D. This study also showed that the injection showed myeloproliferative disorder in the mice bone marrow cells. The FLT3 mutations result in the disruption of the kinase activity. These preclinical studies give researchers a great idea on the responsibility of FLT3 and how they may be a viable therapeutic target for treatment of AML [12]. Another study shows that FLT3 is highly expressed in mixed lineage leukemia (MLL) rearranged acute lymphoblastic leukemia [13]. Acute lymphoblastic leukemia (ALL) is in infants and is categorized by the rearrangements of the mixed lineage leukemia gene, drug resistance, and a poor treatment outcome. In this study, they show FLT3 expression in infants with MLL are higher compared to both infant and noninfant patients with ALL carrying MLL genes. The leukemic cells from infants with MLL are more sensitive to the FLT3 inhibitor than noninfant ALL cells. Their results found the use of flt3 inhibitors could be used in infants with MLL cells since they show with overexpression of FLT3. In the experiment, they assessed whether the level of expression of FLT3 was sufficient enough to self-phosphorylate and activate FLT3 in the absence of activating mutations. They examined several infant MLL and noninfant ALL patients with varying levels of FLT3 expression (Figure 3A). They also analyzed the patients expressing high levels of FLT3 were sensitive to the FLT3 Inhibitor drug, PKC412. Similarly, the

Context in source publication

Context 1

... is involved in leukemic progression. This mutation is shown in Figure 2 on the right. The figure shows the presence of the ligand on FLT3-ITD will activate AKT phosphorylation and increased MAPK activation. ...