Medknow Publications on behalf of Indian Society of Human Genetics
Abstract
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)