FLT3 Gene Involvement in B-cell Acute Lymphoblastic Leukemia (B-ALL).

OBJECTIVES The FMS-like tyrosine kinase 3 gene (FLT3) is a receptor tyrosine kinase expressed in early hematopoietic progenitors that play an important role in hematopoietic development. The signaling pathways that are stimulated by the FLT3 protein manage several crucial cellular processes including division, growth, and survival of cells, specifically of hematopoietic progenitor cells. Activating mutations of this gene have been highly discussed in myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, FLT3 mutations are also observed in around 5% of acute lymphoblastic leukemia (ALL) patients. These mutations were usually found to be one of the four types: internal tandem duplications, tyrosine kinase domain mutations, juxtamembrane insertion and deletion, and juxtamembrane point mutation. The presence of FLT3 mutations in pediatric B-ALL patient populations tend to be associated with relapse and poor prognosis. These mutations are also correlated with poor prognosis in adult B-ALL patients. Due to the rarity of FLT3 mutations in B-ALL patients, there have been many challenges in attempts to understand their role in pathogenesis. In this review, we will discuss the most recent literature and trends associated with FLT3 mutations in B-ALL patients in order to elucidate their cytogenetic, molecular, and clinical implications.