Fms-like tyrosine kinase-3 (FLT3) is a Type III receptor tyrosine kinase expressed by hematopoietic progenitor cells. FLT3 is also sometimes referred to as FLK2 or CD135. The FLT3 protein exists in two states- membrane bound (160 kDa) and cytoplasmic (140 kDa) (1). The FLT3 ligand induces autophosphorylation of FLT3 which allows binding of scaffold and effector molecules. Activated FLT3 is capable of phosphorylating and activating PI3K, PLC-γ, Shc, Grb2, and Src (2). FLT3 signaling ultimately activates the AKT and MAPK pathways to promote cell growth and survival. Mutations in FLT3 account for nearly one third of acute myeloid leukemia (AML) cases. The most common FLT3 derangement in AML is an internal tandem duplication (ITD) in the juxtamembrane domain. FLT3-ITD causes constituent activation of FLT3 signaling. Other activating mutations have also been identified, suggesting an important role for FLT3 in leukemogenesis. FLT3 overexpression correlates with a poor prognosis for AML patients and has become an important target for the development of novel therapeutics.
Ravandi et. al. analyzed 85 AML patient samples for levels of FLT3 expression and phosphorylation (3). The group used the FLT3 antibody to assess levels of total FLT3 and phosphorylated FLT3 in each of their samples. Using beads and the FLT3 antibody, the group was able to immunoprecipitate the FLT3 protein from their samples. The levels of total FLT3 were then quantified by flow cytometry and showed no significant variation among samples. Next, the group used a phospho-tyrosine antibody to determine the relative ratio of phospho-FLT3 to total FLT3 in each sample. The group found significantly higher levels of phospho-FLT3 in patients with FLT3 mutations, as expected.
Arora et. al. used the FLT3 antibody to explore the protein-tyrosine phosphatases (PTP) that negatively regulate FLT3 activity (4). The group used the FLT3 antibody to immunoprecipitate FLT3 from their murine samples. They screened 20 different PTP’s and identified DEP-1 as a potential negative regulator of FLT3. The group suggests the need for further studies to elucidate the mechanism of DEP-1 activity and to identify other PTP’s that may be involved in FLT3 regulation.
Meanwhile, Williams et. al. used the FLT3 antibody to assess FLT3 localization in cells treated with Fluvastatin (5). Fluvastatin is an FDA approved cholesterol-lowering drug belonging to the statin class. This group found that Fluvastatin prevented FLT3-ITD localization to the plasma membrane and induced cell death in the FLT3-ITD cells. These results suggest a potential role for statins in AML combination therapy and the need for further investigation.
Novus Biologicals offers FLT3 reagents for your research needs including:
PMIDs:
