Philadelphia chromosome

The Philadelphia chromosome or Philadelphia translocation (Ph) is an abnormal version of chromosome 22 where a part of the Abelson murine leukemia 1 (ABL1) gene on chromosome 9 breaks off and attaches to the breakpoint cluster region (BCR) gene in chromosome 22. The balanced reciprocal translocation between the long arms of 9 and 22 chromosomes [t (9; 22) (q34; q11)] results in the fusion gene BCR::ABL1. The oncogenic protein with persistently enhanced tyrosine kinase (TK) activity transcribed by the BCR::ABL1 fusion gene can lead to rapid, uncontrolled growth of immature white blood cells that accumulates in the blood and bone marrow.

The Philadelphia chromosome is present in the bone marrow cells of a vast majority chronic myelogenous leukemia (CML) patients. The expression patterns off different BCR-ABL1 transcripts vary during the progression of CML. Each variant is present in a distinct leukemia phenotype and can be used to predict response to therapy and clinical outcomes. The Ph is also observed in patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), and mixed-phenotype acute leukemia.