Discovery of the Philadelphia chromosome: a personal perspective

Abstract

Almost 50 years ago, David Hungerford and I noticed an abnormally small chromosome in cells from patients with chronic myelogenous leukemia (CML). This article is a personal perspective of the events leading to the discovery of this chromosome, which became known as the Philadelphia chromosome. As technology advanced over subsequent decades, the translocation resulting in the Philadelphia chromosome has been identified, its role in the development of CML has been confirmed, and a therapy directed against the abnormal protein it produces has shown promising results in the treatment of patients with CML.

Figure 1. Karyotype of an individual with CML.

A chromosomal preparation of cells at the metaphase stage of mitosis was stained with Giemsa, which binds A-T base pairs. The Philadelphia chromosome (the minute, defective chromosome 22 indicated by the right arrow) results from reciprocal translocation between chromosomes 9 and 22. Left arrow indicates portion of chromosome 22 translocated to chromosome 9. Figure reproduced with permission from eMedicine.com (26).