Acute myeloid leukaemia (AML) is a malignant disease, usually resulting from mutation in a multipotent haemopoietic stem cell. Normal polyclonal haemopoietic cells in the bone marrow are replaced by a clone of neoplastic cell with a growth advantage over normal cells and with a pronounced defect in differentiation. There is usually neutropenia, anaemia and thrombocytopenia as a result both of the differentiation defect of the neoplastic cells and of the crowding out of normal cells. Leukaemic cells may also suppress the growth of normal cells. Occasionally AML results from a mutation in a pluripotent haemopoietic stem cell able to give rise to both lymphoid and myeloid cells. In other categories of acute leukaemia the mutated cell that gives rise to the leukaemic clone may be a cell already committed to the granulocyte-monocyte lineages. The point in the stem cell hierarchy where mutations occur in cases of apparently pure erythroid leukaemia and megakaryoblastic leukaemia has not been defined.
Acute myeloid leukaemia usually arises de novo. However, a significant minority of cases represent evolution of a preceding haematological disorder, which may have been a myeloproliferative or myelodysplastic disorder, aplastic anaemia or paroxysmal nocturnal haemoglobinuria; these cases are referred to as secondary AML. Others are therapy-related, following prior administration of cytotoxic drugs or exposure to radiation. Further aetiological factors include benzene and cigarette smoking. AML is more common in men than women. The prevalence rises exponentially with age to about 18/100 000/year above the age of 65 years . The median age of onset is about 65 years.
Clinical manifestations result either from the proliferation of leukaemic cells or from bone marrow failure that leads to a lack of normal cells. Leukaemic cells can infiltrate tissues, leading to hepatomegaly, splenomegaly, skin infiltrates and swollen gums. Tissue infiltration is particularly a feature when there is monocytic differentiation. As an indirect effect of the leukaemic proliferation there may be hyperuricaemia and occasionally renal failure. The lack of normal cells leads to clinical features of anaemia, neutropenia and thrombocytopenia. Thus there may be pallor, fatigue, breathlessness, fever due to opportunistic infections, purpura and visual impairment (due to retinal haemorrhage). In several subtypes of acute leukaemia, particularly but not only acute promyelocytic leukaemia, there is a profound coagulation defect as a result of both disseminated intravascular coagulation (DIC) and increased fibrinolysis. In such patients purpura and haemorrhagic manifestations are much more pronounced and can be life-threatening.
Occasionally patients with AML present with a tumour at an extramedullary site, e.g. soft tissues such as orbit, lymph nodes, or central nervous system (CNS), while the blood and bone marrow are still apparently normal. A tumour of this type is known as a granulocytic sarcoma or a myeloid sarcoma and it is more frequent in AML with differentiation, either granulocytic or monocytic (French–American–British (FAB) M2, M4 and M5 subtypes).