Characteristics of BCR-ABL rearrangement variants in Pakistani patients with chronic myeloid leukemia and acute lymphocytic leukemia

Document Type



Pathology and Laboratory Medicine; Haematology/Oncology


Background: A reciprocal translocation between the long arms of chromosome 9 and 22 [t (9;22) (q 34; q 1.1)] results in the formation of a fusion hybrid gene also called Philadelphia chromosome encodes proteins with a constitutively activated tyrosine kinase activity [1,2]. These proteins being leukemogenic result in Chronic Myeloid leukemia (CML) and Acute lymphoid leukemia (ALL). Breakage in the long arms of chromosome 9 (ABL1 gene) can occur anywhere within a > 300-kb segment at the 5’end of the gene [1]. Site of breakage in chromosome 22 (BCR gene) can occur in different regions within a 5.8kb region known as the major breakpoint cluster region (M-bcr), spanning 5 exons previously known as b1 to b5 but now as exon 12 to 16 [1]. In CML, the breakpoint in the BCR gene mostly (95%) falls within the major break point cluster region with b2a2 at 40 % and b3a2 at 55% [1].
Methods: The number of reported patients was 686 over a period of 2 years and 10 months (from October 2016 to July 2019). Males comprised 58% of the total while females were 42%. The male to female ratio was 1.4:1. The tested patients were divided into 3 major groups according to their age i.e. x < 20, 20>x<50 and x > 50.The mean age was 40.2 years.
Results: Out of the tested 686 patients, 303 were reported to have the BCRABL1 transcript off which 54.2% were males and 45.9% were females. The ratio of patients diagnosed with Chronic Myeloid Leukemia to Acute Lymphoid leukemia was 9.8:1. 9% of the patients had the mutation e1a2 while 32% had b2a2 and 59% were reported with b3a2.
Conclusions: We conclude that the distribution of BCR/ABL transcript types in patients with CML and ALL differs from most, but not all other populations studied. Currently there are no data from studies of CML and ALL in analyzing a comparable number of cases. The underlying mechanism and causes for the sex-depending distribution of the BCR/ABL transcript types remains open to speculation.


Annals of Oncology