FLT3 (Ab-591) Antibody

Antigen Specificity and Development

The FLT3 (Ab-591) Antibody targets the amino acid sequence surrounding Tyr591 (Y-F-Y-V-D), a region vital for FLT3 kinase activity regulation . Key characteristics include:

This antibody does not distinguish between phosphorylated and non-phosphorylated FLT3 but detects total FLT3 levels, making it distinct from phospho-specific variants like Cell Signaling Technology’s #3461, which exclusively recognizes Tyr591-phosphorylated FLT3 .

Biological Context of FLT3 and Tyr591

FLT3 (FMS-like tyrosine kinase 3) is a receptor tyrosine kinase critical for hematopoietic stem cell survival and differentiation. Constitutive activation through mutations like internal tandem duplications (ITDs) or tyrosine kinase domain (TKD) mutations drives leukemogenesis . Tyr591 resides in the juxtamembrane domain, where phosphorylation modulates:

• Kinase activation: Phosphorylation at Tyr591 enhances FLT3 dimerization and downstream signaling .

• Pathologic signaling: Duplication of Tyr591 (DupY591) in FLT3-ITD mutants amplifies STAT5 and MAPK pathways, promoting chemoresistance in AML .

Key Studies Utilizing FLT3 (Ab-591) Antibody

• AML Subtype Characterization:
  In AML patients, DupY591 mutations correlate with elevated Bcl-2 expression and p53 phosphorylation at serines 15, 46, and 392. FLT3 (Ab-591) helped identify these patients via phospho-specific flow cytometry, linking FLT3 signaling to apoptosis evasion .

• Therapeutic Resistance Mechanisms:
  Co-expression of wild-type (WT) FLT3 with mutant FLT3-ITD reduces FLT3 inhibitor efficacy. FL stimulation activates WT-FLT3, bypassing inhibitor effects on mutant FLT3. This antibody enabled tracking of FLT3 expression levels in such models .

Table: FLT3 (Ab-591) in Disease Context

Comparison with Phospho-Specific Antibodies

While FLT3 (Ab-591) detects total FLT3, phospho-specific antibodies (e.g., Cell Signaling #3461) are essential for studying activation status. For example:

• Phospho-FLT3 (Tyr591) Antibody #3461:

  • Detects endogenous Tyr591-phosphorylated FLT3 .

  • Used in studies linking FLT3 activation to STAT5 signaling .

Implications for Targeted Therapy

FLT3 inhibitors like quizartinib and lestaurtinib show reduced efficacy in WT/mutant FLT3 co-expressing cells due to FL-mediated WT-FLT3 activation . FLT3 (Ab-591) has been instrumental in:

• Validating FLT3 expression in preclinical models.

• Identifying patient subsets with DupY591 mutations for tailored therapies .