Chronic Myeloid Leukemia - Peripheral Blood
Chronic myeloid leukemia (CML) is a myeloproliferative disorder arising from a single genetic translocation in a pluripotential hematopoietic stem cell producing a clonal overproduction of the myeloid cell line. CML is characterized by marked leukocytosis, basophilia, and a dramatic left shift with a predominance of myelocytes, myeloid bulge.
CML has three phases a chronic clinical phase, accelerated phase, and terminates as an acute leukemia in the blast phase. The Philadelphia chromosome is associated in virtually all cases (95%) of CML and must be identified to confirm the diagnosis.
CML is primarily a disease of adults and is predominantly in males over 70 years of age. Symptoms associated are usually minimal and include fatigue, anorexia, abdominal bloating, weight loss, night sweats, dyspnea, pallor, spontaneous bleeding, lymphadenopathy, hepatomegaly, and blurry vision. Some patients are asymptomatic and diagnosis is made incidentally during routine blood testing.
CML can progress to a blast phase defined by >20% blasts in the peripheral blood or bone marrow or by an extramedullary blast proliferation. The blast lineage may be myeloid or lymphoid.
Chronic Myeloid Leukemia - Bone Marrow
Hypercellularity with a very high Myeloid:Erythroid ratio (up to 50:1) and an increase in neutrophils and neutrophil precursors as a result of increased production of myeloid cells. Normoblasts appear reduced in number. Megakaryocytes are normal or increased in number, may appear in clusters, and are often small with reduced nuclear size and reduced nuclear lobulations ("dwarf megakaryocytes"). Reticulin fibers can be increased and the presence of pseudo-Gaucher cells are common and are associated with intramedullary cell destruction.
Pseudo-Gaucher cells and sea-blue histiocytes can be seen due to increased cell turnover. The macrophage cytoplasm is filled with insoluble lipid pigment, called ceroid, which is thought to represent partially digested globosides derived from cell membranes. As compared to Gaucher cells, these cells stain more intensely blue with Wright-Giemsa and the inclusions are globular rather than fibrillary.
The Philadelphia chromosome resulting from t(9;22) creates a chimeric fusion gene BCR-ABL. The presence and expansion of BCR-ABL is the defining feature of CML, as well as the underlying pathophysiologic abnormality of CML. Ph chromosome resulting from t(9;22) is detected in 90% - 95% of cases.
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