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Chronic Myeloid Leukemia - Causes

Medically Reviewed by Dr. Sunil Shroff, MBBS, MS, FRCS (UK), D. Urol (Lond) on Dec 09, 2016


Causes

95% of CML patients report the presence of a specific marker, the Philadelphia (Ph) chromosome.


CML is characterized by the presence of a specific marker, a chromosomal abnormality called the Philadelphia (Ph) chromosome. Approximately 95% of those suffering from CML harbor this abnormality. The Ph chromosome results from a translocation of genes located on the long arms of chromosomes 9 and 22.

[Schematic representation of 9:22 translocation. der9 -> chromosome 9 with extra translocated segment; ph1 -> Philadelphia chromosome.]

The 9:22 translocation brings two different genes together- the breakpoint cluster region gene (BCR),on chromosome 22 and the Ableson leukemia virus gene (ABL), a proto- oncogene, on chromosome 9. The resulting hybrid gene, the BCR-ABL codes for a protein, endowed with tyrosine kinase activity, which has the ability to activate signal transduction pathways. This protein fosters uncontrolled cell proliferation and genomic instability.

In mouse models a CML-like disease has been induced on administering bone marrow cells infected with a BCR-ABL gene-containing virus. In other animal models, the fusion proteins have been shown to transform normal progenitor blood cells to malignant cells.

The other risk factors involved in the onset of CML, irrespective of the Philadelphia chromosome, are the following:

Reference:

  1. SUMMARY OF SPECIFIC SITES OF CANCER - (http://www.canceratlasindia.org/chapter6.asp)

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