Acute leukaemia is a malignant clonal expansion of a haemopoietic progenitor cell.
- it results from distinct but cooperating genetic mutations which give a proliferative and survival advantage to the cells while impairing differentiation and apoptosis (1).
- the immature blasts forms have a prolonged generation time and gradually replace normal bone marrow elements.
Damage to the cell's genetic programme is probably the result of multiple separate events. Rarely is the cause of leukaemia in an individual is obvious. Several environmental exposures, inherited conditions and acquired disorders are implicated in the development of acute leukaemia and include the following:
- environmental exposures to
- chemotherapy
- there are two main types of AML associated with chemotherapy
- exposure to alkylating agents - seen 5-10 years after therapy
- exposure to drugs such as doxorubicin and etoposide - seen 1-5 years after treatment
- ionizing radiation -
- people who have survived atomic bombs and who work in nuclear plants are at an increased risk (not people living near nuclear plants)
- less confirmed source of radiation exposure is seen in pilots of commercial jet planes. An increased incidence of AML was observed in Danish male cockpit crew who had flown for over 5000 hours
- exposure to chemicals that include petroleum products and organic solvents (benzene), herbicides, and pesticides (organophosphates)
- the most common source of benzene exposure is cigarette smoking
- there is an increased incidence of AML in smokers with the greatest risk in current smokers
- inherited conditions
- in children several inherited conditions predispose to the development of AML
- Down syndrome, Fanconi anemia, severe congenital neutropenia (Kostmann syndrome), Bloom syndrome, neurofibromatosis type 1, Noonan syndrome, Klinefelter’s syndrome,
- acquired conditions
- aplastic anemia, myelodysplastic syndrome, acquired amegakaryocytic thrombocytopenia, paroxysmal nocturnal hemoglobinuria (1).
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