Derived from the relocation of c-ABL gene from chromosome 9 to the portion of BCR gene locus on chromosome 22.
Breakpoint cluster region/Abelson murine leukemia viral proto-ontogeny.
Codes for an abnormal non-membrane bound oncoprotein, an active tyrosine kinase impacting signal transduction pathways with reduction in apoptosis and uncontrolled cell proliferation.
The BCR: ABL1 fusion gene codes an active tirosine kinase that drives the onset of CML.
Most frequently has a molecular weight of 210 kD with increased kinase activity, essential to its transf2241ing capabilities.
The BCR-ABL oncogene codes for the BCR/ABL protein, which is a tyrosine kinase that is specific to leukemic cells.
Activation of signaling pathways by p210 BCR/ABL is mediated through the SRC family kinases.
The BCR-ABL1 fusion protein is a tyrosine kinase, an enzyme with the ability to phosphorylate proteins.
May acquire new mutations leading from chronic phase to acute phase and involve p53 gene, loss of p16, INK-41/ARFEXON-2 and changes in RB.
Present in most patients with CML and is a cohort of ALL patients.
Occurs in about a quarter to the third of adult patients with ALL.
Present in approximately 30-40% of adults with B-cell acute lymphoblastic leukemia.
Unregulated tyrosine kinase activity of this protein leads to CML and Philadelphia positive ALL.
Stimulates signaling pathways that induce growth factor independence, affects adhesive and invasive capabilities of leukemic cells.
Modulates responses to DNA damage rendering cells resistant to genotoxic therapy and causes genomic instability.
Instability may lead to mutations and chromosomal translocations that occur during transition frequently observed during the transition from chronic CML to aggressive blast crisis.
Imatinib (Gleevec) is a BCR-ABL tyrosine kinase inhibitor which can induce remissions in CML.
Instability also is manifested by mutations detected in the BCR/ABL gene encoding for resistance.