What causes pediatric acute myelocytic leukemia (AML)?

Updated: Sep 12, 2017
  • Author: Mark E Weinblatt, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Although the cause of acute myeloid leukemia is unknown in most patients, several factors are associated with its development. Despite these correlations, most people exposed to the same factors do not develop leukemia. This pattern suggests that these factors trigger the malignant transformation of cells, perhaps due to the action of one or more oncogenes or tumor suppressor genes. Defects in deoxyribonucleic acid (DNA) repair mechanisms also contribute to the development of acute myeloid leukemia.

Acute leukemia is believed to begin in a single somatic hematopoietic progenitor that transforms to a cell incapable of normal differentiation. Acute myeloid leukemia is a very heterogeneous disease from a molecular standpoint; oncogenic transformation into a leukemic stem cell may occur at different stages of normal hematopoietic cellular maturation, from the most primitive hematopoietic stem cell to later stages, including myeloid/monocytoid progenitor cells and promyelocytes. This determines which subtype of acute myeloid leukemia results, often with very different behavior and growth characteristics.

As opposed to acute lymphoblastic leukemia (ALL), acute myeloid leukemia is most commonly associated with the development of fusion genes resulting from chromosome translocations. Many translocations are characteristic of a particular subtype of acute leukemia and often convey additional prognostic information to the clinician. Although many patients have only a single cytogenetic abnormality, multiple genetic mutations are often required for the complete leukemic transformation.

Many of the leukemic cells no longer possess the normal property of apoptosis, or programmed cell death. As a result, they have a prolonged life span and are capable of unrestricted clonal proliferation. Because transformed cells lack normal regulatory and growth constraints, they have favorable competitive advantage over normal hematopoietic cells. The result is the accumulation of abnormal cells with qualitative defects. The major cause of morbidity and mortality is the deficiency of normally functioning, mature hematopoietic cells rather than the number of malignant cells.

Splenomegaly due to leukemic infiltration may further contribute to pancytopenia by sequestering and destroying circulating erythrocytes and platelets. As the disease progresses, signs and symptoms of anemia, thrombocytopenia, and neutropenia increase.

Leukemic cells may infiltrate other bodily tissues, causing many clinically significant complications, including CNS involvement, pulmonary dysfunction, or skin and gingival infiltration.

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