Acute Myelogenous Leukaemia

Abstract Acute myelogenous leukaemia is the result of a malignant transformation of a single primitive multipotential marrow haematopoietic cell, converting it to a leukaemic stem cell. This neoplastic transformation imparts a growth and survival advantage to the cell clone that emerges. Leukaemic cells fill the haematopoietic cords of marrow. The functional result of this alteration is to impair normal blood cell production in the marrow, leading to a profound decrease in normal red cells (anaemia), white cells (leucopaenia) and platelets or thrombocytes (thrombocytopaenia) in the blood. The disease is rapidly progressive, unless treated promptly. Therapy usually consists of at least two drugs, cytosine arabinoside and an anthracycline antibiotic (e.g. daunomycin). The response of the disease to treatment is dependent on several factors but the two most compelling are the age at diagnosis and the cytogenetic and genetic features of the cells with older age and unfavourable chromosomal karyotypes decreasing the proportion of long‐term remissions. Key Concepts: Cancer of any type is the result of a series of gene mutations in a single tissue cell. Acute myelogenous leukaemia, like all cancers, originates in a single tissue cell, in this case within haematopoietic tissue. The incidence of acute myelogenous leukaemia can be increased by the inheritance of predisposition genes that are unapparent (nonsyndromic familial cases) or apparent as manifest by syndromic cases, such as Fanconi anaemia. Leukaemic cells accumulate because they have a proliferative and survival advantage compared to normal cells. It is estimated that approximately one trillion leukaemic cells are present at diagnosis. Very small proportions of these cells are leukaemic stem cells, which sustain leukaemic haematopoiesis. Acute myelogenous leukaemia stem cells have multipotential haematopoietic lineage potential. Thus, they can differentiate into leukaemic precursor cells of all haematopoietic lineages. The predominance of one or two leads to the phenotypic classification of acute myelogenous leukaemia (e.g. erythroid, monocytic, megakaryocytic and myelomonocytic). The accumulation of leukaemic cells in the marrow secondarily suppresses normal blood cell development. Chemotherapy is predicated on the coexistence of normal haematopoietic stem cells and leukaemic stem cells in the marrow. Suppression of leukaemic cell accumulation by at least three logs by chemotherapy can, in many cases, result in the release of inhibition of normal stem cells and a return of normal haematopoiesis for a variable time.