Philadelphia Chromosome: used with permission from Macmillan Cancer Support
An abnormal chromosome known as the Philadelphia Chromosome is present in over 90% of CML cases. This particular aberration is caused by a translocation between the long arms of chromosomes 9 and 22. The abnormality is described as t(9;22)(q34;q11.2) in cytogenetic notation. The translocation involves the tyrosine kinase coding region within the ABL gene on chromosome 9 and the BCR gene from chromosome 22. This rearrangement results in a fusion gene called BCR/ABL1, which is located on chromosome 22 (see image). Several abnormal mechanisms arise from this abnormal chromosome, although the increase in tyrosine kinase activity is attributed to abnormal production of clonal hematopoietic cells.
Since most cases of CML demonstrate the Philadelphia chromosome, identification of this cytogenetic abnormality or the BCR/ABL1 fusion gene is extremely helpful in the diagnosis of the disease. It is important to note that the Philadelphia chromosome is not specific to CML. It is also found, although much less commonly, in cases of acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) as well.