Chromosome 7 and Haematological Malignancies

Abnormalities of chromosome 7 are the most common clonal chromosomal changes observed in myelodysplasia (MDS) and the second most frequent in acute myeloid leukaemia (AML) [1-5]. These changes may consist of long arm deletion (7q-) or total loss of the whole chromosome (monosomy 7) from bone marrow cells [1, 4, 6-24] and was first reported in association with myeloid disease in 1964 with the report of 3 cases of refractory anaemia, granulocytic hyperplasia [25]. The association between chromosome 7 alterations, MDS and AML in children and adults is clear, however, a rare association with lymphoid malignancies has also been recently reported. The abnormalities may occur in de novo MDS/AML, secondary cases following exposure to drugs, radiotherapy and toxins and in addition in a range of constitutional disorders including Fanconi's anaemia, congenital neutropenia and neurofibromatosis type 1 (NF1). The broad spread of conditions in which this consistent genetic change can occur leads one to speculate that there is an underlying instability in chromosome 7 and that genes on this chromosome play a role in the development of malignancy. The loss of DNA associated with malignant progression suggests the presence of a tumour suppressor gene (or genes) [26, 27]. Patients with monosomy 7 usually present as classical MDS with abnormal erythroid, megakaryocyte and myeloid differentiation [7, 28]. From a mechanistic perspective, increased cell proliferation and apoptosis is a common feature possibly induced by the failure of normal haematopoietic maturation. In all groups the presence of chromosome 7 abnormalities defines a poor prognostic group [29]. The majority of patients with MDS transform to a form of acute leukaemia resistant to therapy, including bone marrow transplantation (BMT). Although fluorescence in situ hybridization (FISH) has accelerated the study of these disorders at the cytogenetic and molecular levels, [4, 30, 31, 32, 33] no gene has been clearly implicated. A few candidate genes are under investigation. While the loss of chromsome 7 material is crutial in the malignant process it is almost certainly not the primary molecular abnormality. An initiating event genetic event predisposing to chromosome breakage and loss probably occurs in haematopoietic cells permitting chromosome 7 loss and progression to clonal malignancy as a secondary event.