Review Article - Chronic Myeloid Leukemia: Cytogenetics and Molecular Genetics

Chronic myelogenous leukemia (CML) is a pleuripotent stem cell disorder characterized by proliferation and accumulation of mature myeloid cells and their progenitors. It is a first human malignancy where a specific marker- the Philadelphia (Ph) chromosome was linked to pathogenetic events of leukemogenesis. Around 99% of CML cases are Ph positive which include 91%-96% of cases with standard Ph resulting from a reciprocal translocation between long arm of chromosome 9 and 22 (Rowley, 1973) (Fig. 1); and 3%-8% of cases with variant or masked Ph (Rowley, et al. 1982; Kadam, et al. 1990; Bernstein, et al. 1984). Ph chromosome is also found in 5% of children and 15%-30% of adults with acute lymphoblastic leukemia (ALL) and around 2% - 6% of patients with acute myeloblastic leukemia (AML) (Kurzrock, et al. 1988; Specchia, et al. 1995; Kadam, et al. 1991) ). At gene level break occurs in ABL and BCR gene on chromosome 9 and 22 respectively, with the result the 22q11 -> qter segment including part of the BCR gene is translocated to ABL locus on chromosome 9 and reciprocally 3' segment of ABL gene is transposed and inserted to 5' segment of BCR gene on chromosome 22 (Fig. 2). The resulting BCR-ABL fusion on Ph chromosome is transcribed in to a chimerical RNA and then translated in to a fusion protein of varying size-p210, p190 (Fig. 2).