An abnormal chromosome known as the Philadelphia Chromosome is present in over 90% of CML cases. This 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 as shown in the image. Several abnormal mechanisms arise from this abnormal chromosome, although the increase in tyrosine kinase activity is attributed to the abnormal production of clonal hematopoietic cells.
Since most cases of CML demonstrate the Philadelphia chromosome, identifying this cytogenetic abnormality or the BCR-ABL1 fusion gene is extremely helpful in diagnosing 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 acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) cases.
