FLT3 and BCR-ABL1

FLT3 (FMS-like tyrosine kinase 3) is a member of the class III receptor tyrosine kinase family, primarily expressed on hematopoietic progenitor cells, where it regulates cell proliferation, survival, and differentiation[1][5][6]. Mutations, especially internal tandem duplications (ITD) or tyrosine kinase domain (TKD) point mutations, lead to constitutive receptor signaling and play a central oncogenic role in acute myeloid leukemia[2][6]. BCR-ABL1 is a constitutively active fusion oncoprotein generated by the reciprocal translocation t(9;22)(q34;q11), forming the Philadelphia chromosome[3][7]. This fusion protein encodes a deregulated tyrosine kinase that drives malignant transformation via enhanced proliferation and survival signaling, and is the hallmark molecular lesion of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)[3][4][7].

Other names

CD135FLK2STK-1Philadelphia chromosomePh+ fusion proteinp210 BCR-ABLp190 BCR-ABL

For FLT3: Small molecule inhibitors bind to the FLT3 kinase domain, inhibiting its constitutive phosphorylation and signaling. For BCR-ABL1: Tyrosine kinase inhibitors (TKIs) block the ATP-binding site of the fusion kinase, preventing aberrant signaling.