The Philadelphia Chromosome

Posted on Mar 27, 2013 in Cellular, Editorial, Illustration, Molecular

The Philadelphia Chromosome

This illustration was created for JAAPA, February 2013 • 26(2).

The Philadelphia chromosome is formed when a piece of chromosome 9 exchanges places with a piece of chromosome 22, resulting in a balanced translocation t(9;22)(q34;q11) and the formation of an abnormal fusion gene BCR-ABL1.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The American Cancer Society estimated that in 2012, the number of newly diagnosed CML cases would be 5,430, with 610 deaths.1 The discovery of the tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment and prognosis of CML, making imperative early recognition of CML. Timely diagnosis will ensure that patients receive early treatment, significantly improving their prognosis.

CML is caused by a cytogenetic abnormality that is thought to be acquired and involves a balanced translocation between chromosome 9 and chromosome 22. The BCR gene on chromosome 22 fuses with the ABL1 gene on chromosome 9, resulting in the abnormal fusion gene BCR-ABL1 located on chromosome 22 (Figure 1). The fusion gene produces a protein with tyrosine kinase activity that causes cells to proliferate. The resultant abnormal chromosome 22 [t(9;22)(q34;q11)] is also known as the Philadelphia (Ph) chromosome. It is identified in 95% of patients with CML and can be detected in all myeloid cells, including granulocytes, erythrocytes, monocytes, and B lymphocytes