Molecular and cytogenetic abnormalities in acute myeloid leukaemia and myelodysplastic syndromes

Acquired chromosomal changes are a characteristic of all tumour cells. In this chapter we shall briefly review the cytogenetic abnormalities that are more specifically associated with acute myeloid leukaemia (AML) and the myelodysplastic syndromes (MDS). Their clinical usefulness and their significance for the understanding of the mechanism of leukaemogenesis will be discussed. Mitotic abnormalities had already been discovered in tumour cells by the end of the last century (Arnold, 1879). Boveri (1914) was the first to suggest the existence of a relationship between the abnormal chromosome pattern and the malignant phenotype of the cells. Nowell and Hungerford (1960) reported the constant presence of a small marker chromosome, known as the Philadelphia chromosome, in patients with chronic myeloid leukaemia (CML). With the use of banding techniques (Caspersson et al, 1970; Hagemeijer et al, 1979) recurrent patterns of numerical or structural chromosome abnormalities were found to correlate with distinct haematological malignancies. At several International Workshops on Chromosomes in Leukaemia, defined correlations were found between cytogenetic abnormalities, morphology and immunophenotype, clinical, epidemiological and aetiological factors, as well as prognostic implications for therapeutic response and survival. The development of molecular genetics in the 1980s led to the characterization of the genes involved in the cytogenetic abnormalities. These studies revealed a new mechanism of oncogenesis by illegitimate gene fusion, as a consequence of translocation, Information was, and still is, obtained on the different molecular mechanisms and changes leading to malignant transformation. In addition, these analyses provide insight into the genetic control of normal haematopoiesis.