Monosomy 7 and 7q- associated with myeloid malignancy

Abstract

An association between the complete or partial loss of chromosome 7 and preleukaemic myelodysplasia or acute myeloid leukaemia has been recognized from the early days of tumour cytogenetic analysis. Detection of such abnormalities usually heralds a poor prognosis. The loss of DNA on chromosome 7 has led to speculation that tumour-suppressor genes may play a significant role in this form of leukaemogenesis, although it may be part of a multistep process. A further association with leukaemia secondary to carcinogen exposure including previous chemotherapy or a number of congenital anaemias has increased the interest in discovering the gene or genes on chromosome 7. Banded chromosome analysis has suggested that there are two broad critical regions on the long arm of chromosome 7 at bands 7822 and 7q34–q36 that may contain the relevant genes. Initial molecular analysis has confirmed these to regions to be of significance. The advent of fluorescence in-situ hybridization techniques has facilitated some definition of the 7g22 region, with identification of candidate genes for further functional analysis. It is becoming clear that there will be more than one gene on chromosome 7 involved in the leukaemic process and with the definition of these genes it may be possible to look for associations with different phenotypes and prognosis. As for the reason for chromosome 7 showing a particular predisposition to total or partial loss we may speculate that the DNA sequence and structure may confer a `fragility' on the chromosome. A greater understanding of the DNA structure of the long arm may provide real insight into the mechanisms of leukaemia. We would like to speculate in the long term that this could lead to the ability to screen for leukaemia susceptibility and avoidance of ‘inducers’ in those at risk.