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  • Elevated white blood cell count.

  • Markedly left-shifted myeloid series but with a low percentage of promyelocytes and blasts.

  • Presence of bcr/abl gene (Philadelphia chromosome).


CML is a myeloproliferative disorder characterized by overproduction of myeloid cells. These myeloid cells continue to differentiate and circulate in increased numbers in the peripheral blood.

CML is characterized by a specific chromosomal abnormality and a specific molecular abnormality. The Philadelphia chromosome is a reciprocal translocation between the long arms of chromosomes 9 and 22. The portion of 9q that is translocated contains abl, a protooncogene that is received at a specific site on 22q, the break point cluster (bcr). The fusion gene bcr/abl produces a novel protein that possesses tyrosine kinase activity. This disorder is the first recognized example of tyrosine kinase “addiction” by cancer cells.

Early CML (“chronic phase”) does not behave like a malignant disease. Normal bone marrow function is retained, white blood cells differentiate, and despite some qualitative abnormalities, the neutrophils combat infection normally. However, untreated CML is inherently unstable, and without treatment, the disease progresses to an “accelerated” phase and then an “acute blast” phase, which is morphologically indistinguishable from acute leukemia.


A. Symptoms and Signs

CML is a disorder of middle age (median age at presentation is 55 years). Patients usually complain of fatigue, night sweats, and low-grade fevers related to the hypermetabolic state caused by overproduction of white blood cells. Patients may also complain of abdominal fullness related to splenomegaly. In some cases, an elevated white blood count is discovered incidentally. Rarely, the patient will present with a clinical syndrome related to leukostasis with blurred vision, respiratory distress, or priapism. The white blood count in these cases is usually greater than 100,000/mcL (100 × 109/L) but less than 500,000/mcL (500 × 109/L). On examination, the spleen is enlarged (often markedly so), and sternal tenderness may be present as a sign of marrow overexpansion. In cases discovered during routine laboratory monitoring, these findings are often absent. Acceleration of the disease is often associated with fever (in the absence of infection), bone pain, and splenomegaly.

B. Laboratory Findings

CML is characterized by an elevated white blood cell count; the median white blood count at diagnosis is 150,000/mcL (150 × 109/L), although in some cases the white blood cell count is only modestly increased (Table 13–14). The peripheral blood is characteristic (eFigure 13–23). The myeloid series is left shifted, with mature forms dominating and with cells usually present in proportion to their degree of maturation. Blasts are usually less than 5%. Basophilia and eosinophilia may be present. At presentation, the patient is usually not anemic. Red blood cell morphology is normal, and nucleated red blood cells ...

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