See Etiology in General Leukemia
Pathogenesis
Leukemic cells have:
- Proliferation and survival advantages
- Impaired differentiation
Proteins altered in AML are in 2 distinct functional groups:
1. Proteins involved in proliferation and survival:
- Activated tyrosine kinases (such as FLT3 and c-KIT) give proliferative and survival signals to leukemic blast cells.
2. Proteins involved in differentiation
- Alteration of proteins involved in transcriptional regulation such as core binding factor (CBF), retinoic acid receptor alpha, MLL and HOX leads to impaired differentiation.
Leukemic phenotype probably requires the presence of both types of mutation in the same cell.
Conditions associated with an increased risk of AML:
- Genetic and constitutional:
- Prenatal Factors:
- Parental exposure to pesticides, solvents or petroleum products
- Maternal alcohol consumption and marijuana use
- Postnatal Factors:
- Exposure to pesticides and petroleum products
- Cytotoxic chemotherapy
- Radiation exposure
- Aplastic anemia
