Abstract

Chronic myeloid leukemia is a molecular fault from neoplastic transformation of hematopoietic stem cells. It is elicited by an extensive spectrum of “fused oncoproteins” which are necessitated in the disease refractoriness. It docks a miscellany of fusion transcripts originating from chromosomal rearrangements. Additionally, vulnerability to genomic rearrangements is particularly enhanced in chronic myeloid leukemia which is triggered by BCR-ABL fusion gene. The hallmark genetic abnormality of chronic myeloid leukemia is at t (9; 22) (q34; q11) transformation fallouts into small Philadelphia chromosome. Three types of proteins are encoded by BCR-ABL oncogene such as p230, p210 and p190. 210 kilodalton dysregulated tyrosine kinase (p210) is indispensable and adequate for leukaemogenesis. BCR-ABL oncoprotein contains specific domains for the activation of signal transduction. Presently there are below par measures to demarcate this rapidly growing threat. The review will cover various mechanistic insights of the BCR-ABL genomic instability. Moreover effectiveness of therapeutic interventions recently designed keeping in view the molecular hierarchy will be evaluated.

Key words: Chronic myeloid leukemia, imatinib, break point cluster region- c-Abelson (BCR-ABL).

Abbreviation

AKT: AKT protein, Bcl-2: Bcl-2 protein, BclXL: B-cell lymphoma-extra large, BCR-ABL: break point cluster region- c-Abelson, CK-2: casine kinase-2, CML: chronic myeloid leukemia, c-Myc: myelocytomatosis, Cyc D: cyclin D, ERK: extracellular signal regulated kinase, GAB2: GRB2-associated binding protein 2, GRB2: growth factor receptor-bound protein 2, MAP-kinase: mitogen activated protein-kinase, Ph: Philadelphia chromosome, PI3K: phosphoinositol-3 kinase, Ras: ras protein, SH2: SRC homology domain 2, SH3: SRC homology domain 3, SOS: Son of sevenless protein, STAT: Signal transducer and activator of transcription.