Chronic Myelogenous Leukemia
Chronic Myelogenous Leukemia (CML, Chronic Granulomatous Leukemia)
disorder characterized by the massive overproduction of granulocytes, the presence of a specific chromosomal marker (the Philadelphia chromosome), and the inevitable transformation into acute leukemia.
Etiology – unknown, radiation?
Median age – mid 40’s
Incidence – 1/100,000 U.S. population; 20% of all leukemias
Clinical features: asymptomatic or fatigue, fever, night sweats; splenomegaly; median duration 3 yrs
Ý WBC with immature granulocytes in circulation; leukocytosis, thrombocytosis; mild anemia (normochromic, normocytic)
Hyperplastic marrow with normal maturation; 20 to 40% show Ý marrow fibrosis
Philadelphia chromosome (diagnostic feature), t(9;22) – found in all patients with CML; breakpoint in Chr 9 is at ABL gene and in Chr 22 at BCR gene Þ BCR next to ABL on Chr 22 Þ "always on" tyrosine kinase activity Þ blocks apoptosis, ß adhesiveness to stromal cells in marrow Þ CML
ß LAP (leukocyte alkaline phosphatase – diagnostic feature); Ý B12 and B12BC (B12 binding protein)
a-interferon – controls cell counts and can suppress the philadelphia clone; prolongs survival of CML patients
bone marrow transplantation (best therapy) – only treatment that is curative – only applicable to 10 to 15 % of patients who are young and have HLA matched donors.
: worsening symptomology; Ý splenomegaly; extramedullary leukemia
lab features: Ý anemia; thrombocytopenia; Ý % blasts (block in maturation occurs); new chromosomal abnormalities; Ý LAP score; disease terminates in blast phase which resembles acute leukemia (myeloblastic or lymphoblastic)
- hydroxyurea/busulfan – oral cytotoxic agents; symptomatic treatment
- anti-leukemic chemotherapy – generally unsuccessful
- ? new approaches (STI571 – specifically blocks BCR-ABL tyrosine kinase) – thus far shown to be effective in treating patients with chronic phase CML and its being studied in patients with more advanced disease.