A 38-year-old male presents with increasing weakness and is found to have a markedly elevated peripheral leukocyte count. Laboratory testing on peripheral blood finds a decreased leukocyte alkaline phosphatase (LAP) score, while chromosomal studies on a bone marrow aspirate find the presence of a Philadelphia chromosome. This abnormality refers to a characteristic chromosomal translocation that involves the oncogene

Chronic myeloid leukemia (CML) is one of the four chronic myeloproliferative disorders, but, unlike myeloid metaplasia or polycythemia vera, CML is associated with the Philadelphia chromosome translocation t(9;22) in over 90% of cases. This characteristic translocation, which involves the oncogene c-abl on chromosome 9 and the breakpoint cluster region on chromosome 22, results in the formation of a new fusion protein (P210) that is a non-receptor tyrosine kinase. In differentiating CML from a leukemoid reaction, several other features are impoant in addition to the presence of the Philadelphia chromosome: lack of alkaline phosphatase in granulocytes, increased basophils and eosinophils in the peripheral blood, and, often, increased platelets in early stages followed by thrombocytopenia in late or blast stages. Other well-known features of CML include marked splenomegaly, leukocyte counts greater than 50,000/uL, and mild anemia. Reference: Robbins & Cotran Pathologic Basis of Disease, 9edition.