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Clinical manifestations and diagnosis of chronic myeloid leukemia

Richard A Van Etten, MD, PhD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Chronic myeloid leukemia (CML, also known as chronic myelocytic, chronic myelogenous, or chronic granulocytic leukemia) is a myeloproliferative neoplasm characterized by the dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation. (See "Overview of the myeloproliferative neoplasms".)

CML is associated with the fusion of two genes: BCR (on chromosome 22) and ABL1 (on chromosome 9) resulting in the BCR-ABL1 fusion gene. This abnormal fusion typically results from a reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), that gives rise to an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. It is this derivative chromosome 22 which harbors the BCR-ABL1 fusion gene.

The BCR-ABL1 fusion gene results in the formation of a unique gene product, the BCR-ABL1 fusion protein. This protein product includes an enzymatic domain from the normal ABL1 with tyrosine kinase catalytic activity, but relative to ABL1, whose kinase activity is tightly regulated [1], the kinase activity of BCR-ABL1 is elevated and constitutive [2] due to fusion with a portion of BCR. It is this deregulated tyrosine kinase that is implicated in the pathogenesis of CML. (See "Molecular genetics of chronic myeloid leukemia".)

The clinical hallmark of CML is the uncontrolled production of mature and maturing granulocytes, predominantly neutrophils, but also basophils and eosinophils. In the absence of treatment, CML has a triphasic or biphasic clinical course as it progresses from a chronic phase to an accelerated phase and on to a terminal blast crisis. Sometimes it goes from chronic phase directly to blast crisis, particularly when the blast phase is lymphoid.

The clinical manifestations and diagnosis of CML will be reviewed here. The molecular genetics, biology, and treatment of this disorder are considered separately. (See "Molecular genetics of chronic myeloid leukemia" and "Cellular and molecular biology of chronic myeloid leukemia" and "Overview of the treatment of chronic myeloid leukemia".)

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Literature review current through: Nov 2017. | This topic last updated: Apr 10, 2017.
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