Immunological and genetic abnormalities in chronic lymphocytic leukaemia. Impact of the purine analogues

Drugs
G Juliusson

Abstract

Chronic lymphocytic leukaemia (CLL) is a disease characterised by several immune defects such as frequent autoimmune complications and functional T-cell defects, which lead to an increased risk of infections (mostly bacterial) and other tumours. Clonal chromosome abnormalities are identified in half of the patients, and trisomy 12, the most common aberration, is present in about one-third of patients with clonal changes. The commonest structural abnormalities involve chromosome 13 at band q14, the site of the retinoblastoma tumour suppressor gene. A gene located telomeric to the Rb1 gene, identified by the D13S25 probe, might be a better candidate for a pathophysiologically relevant gene in CLL, since repeated reports have identified homozygous deletions of this site. The purine analogues fludarabine and cladribine (2-chloro-2'-deoxyadenosine) and the adenosine deaminase inhibitor deoxycoformycin all have therapeutic effects in a range of lymphoproliferative disorders. Prolonged immunosuppression with low CD4 cell counts frequently occurs and, subsequently, opportunistic infections may be seen. This has to be taken into consideration when treating patients with any of these potent drugs.

Citations

Dec 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D Catovsky, R L Murphy
Dec 13, 2012·International Urology and Nephrology·Yao-Ko Wen, Kai-I Wen
Oct 1, 1996·Leukemia & Lymphoma·D CatovskyJ A Garcia-Marco
Aug 16, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·V A MorrisonC A Schiffer

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