Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the prevention and cessation of cigarette smoking and the control of tobacco use. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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(Refer to the PDQ summary on Chronic Myeloproliferative Disorders Treatment for more information.)
CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1).[2,3] The Ph1 results from a reciprocal translocation between the long arms of chromosomes 9 and 22 and is demonstrable in all hematopoietic precursors. This translocation results in the transfer of the Abelson (ABL) on chromosome 9 oncogene to an area of chromosome 22 termed the breakpoint cluster region (BCR). This, in turn, results in a fused BCR/ABL gene and in the production of an abnormal tyrosine kinase protein that causes the disordered myelopoiesis found in CML. Furthermore, these molecular techniques can now be used to supplement cytogenetic studies to detect the presence of the 9;22 translocation in patients without a visible Ph1 (Ph1-negative).
Ph1-negative CML is a poorly defined entity that is less clearly distinguished from other myeloproliferative syndromes. Patients with Ph1-negative CML generally have a poorer response to treatment and shorter survival than Ph1-positive patients. Ph1-negative patients who have BCR/ABL gene rearrangement detectable by Southern blot analysis, however, have prognoses equivalent to Ph1-positive patients.[6,7] A small subset of patients have BCR/ABL detectable only by reverse transcriptase–polymerase chain reaction (RT–PCR), which is the most sensitive technique currently available. Patients with RT–PCR evidence of the BCR/ABL fusion gene appear clinically and prognostically identical to patients with a classic Ph1; however, patients who are BCR/ABL-negative by RT–PCR have a clinical course more consistent with chronic myelomonocytic leukemia, which is a distinct clinical entity related to myelodysplastic syndrome.[6,8,9] Fluorescent in situ hybridization of the BCR/ABL translocation can be performed on the bone marrow aspirate or on the peripheral blood of patients with CML.