FUSION GENE BCR-ABL : FROM ETIOPATHOGENESIS TO THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA
Abstract: Chronic Myeloid
Leukemia (CML) is a myeloproliferative neoplasm. CML is relative frequent
disorder. Most of CML patients have Philadelphia chromosome (Ph),which is
derived from a reciprocal translocation between chromosome 9 and 22,
t(9;22)(q34;ql1), generating the BCRABLfusion gene. In general, there are 3
breakpoint cluster regions in BCR gene : mayor(M-bcr), minor (m-bcr) and micro
(μ-bcr). The BCR-ABL gene encodes proteins that vary in size depending on the
breakpoint in the BCR gene. However, these proteins share a high tyrosine
kinase activity. In the absence of activating stimuli, BCR-ABL tyrosine kinase
able to transferphosphate from ATP (autophosphorilation) to tyrosine residues
on various substrates in the cell. It actives intracelluler signaling pathways.
These pathways cause increase proliferation or decrease apoptosis and
differentiation of a hematopoietic stem cell; and defect in adherence of
myeloid progenitors to marrow stroma resulting in CML. These discoveries
determined that BCR-ABL fusion gene is critical event in etiopathogenesis of
CML and a ideal target for therapy. Therapy of CML patients with BCRABL fusion
gene-positif is by block autophosphorilation mechanism by Tyrosine Kinase
Inhibitor (TKI), example imatinib. Molecular method to detect BCR-ABL
transcript is necessary for monitoring response to TKI in CML pateints.
Keywords: CML, BCR-ABL, fusion
gene, autophosphorilation,Tyrosine Kinase Inhibitor
Author: Tri Agusti Sholikah
Journal Code: jpkedokterangg170262