ORIGINAL ARTICLE: CLINICAL The P2X7 receptor gene polymorphism 1513 A!C has no effect on clinical prognostic markers and survival in multiple myeloma SHANKARANARAYANA PANEESHA 1 , JANE STARCZYNSKI 1 , CHRIS PEPPER 2 , JULIO DELGADO 1 , LAURA HOOPER 1 , CHRISTOPHER FEGAN 1 , & GUY PRATT 1,3 1 Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK, 2 Department of Haematology, Wales College of Medicine, Cardiff, UK, and 3 Institute for Cancer Studies, University of Birmingham, Birmingham, UK Abstract A P2X7 receptor gene polymorphism 1513 A!C has recently been suggested as playing a role in the pathogenesis and disease progression of chronic lymphocytic leukemia, although several studies have failed to show any effect of the polymorphism. The effects of this polymorphism were analysed in 136 patients with multiple myeloma. The frequency of the polymorphism in the myeloma samples was not significantly different from that found in normal healthy controls. There was no significant difference in age at diagnosis, creatinine, hemoglobin, b-2 microglobulin, immunoglobulin sub-type, duration of first response and overall survival. These results are in keeping with findings in a cohort of 121 chronic lymphocytic leukemia and do not support a role for this polymorphism in multiple myeloma. Keywords: Multiple myeloma, P2X7, polymorphism Introduction The purinergic P2X7 receptor has recently become the focus of several studies in B-cell chronic lymphocytic leukemia (B-CLL), with evidence for it having a potential role in both cellular growth [1] and in apoptosis [2]. A single nucleotide polymorphism (1513 A!C) was reported to result in loss of function of the receptor [2]. The frequency of this polymorphism was higher in B-CLL patients with indolent disease compared with normal individuals suggesting that the loss of function of the receptor might have an anti-apoptotic effect. In contrast, Thunberg et al. [3] found a significantly higher frequency of the polymorphism in normal controls compared with B-CLL patients and a prolonged survival for B-CLL patients who were heterozygous for this polymorphism compared with homozygous patients. More recently, a possible role for the P2X7 receptor in susceptibility to familial B-CLL has been suggested [4]. However, the incidence of this mutation and its relevance, if any, to the pathogenesis of B-CLL remains controversial. Both the authors and others [5 – 8] have failed to show any association in B-CLL with clinical markers or survival or any difference in the frequency of the polymorphism compared with the normal population. Several polymorphisms in the P2X7 receptor have been described that lead to loss of function of the receptor [9–11], but there is no data looking at whether these polymorphisms have any impact on B-CLL. Multiple myeloma is another mature B cell malig- nancy that, like B-CLL, is characterized by a failure of apoptotic cell death. We, therefore, analysed the effect of the P2X7 1513 A!C polymorphism in 136 multiple myeloma patients Patients and methods This study was a retrospective study looking at unselected myeloma patients attending the outpati- ent clinic at Birmingham Heartlands Hospital. These patients had been diagnosed according to standard morphological and clinical criteria. The study had Local Research Ethical approval and all patients had given informed consent. All patients were treated either as part of a clinical trial (MRC Myeloma VII or VIII studies or UK Myeloma Forum study IX) or Correspondence: Dr Guy Pratt, Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Tel: 0121 4243698. Fax: 0121 7667530. E-mail: guy.pratt@heartofengland.nhs.uk Received for publication 11 August 2005. Leukemia & Lymphoma, February 2006; 47(2): 281 – 284 ISSN 1042-8194 print/ISSN 1029-2403 online Ó 2006 Taylor & Francis DOI: 10.1080/10428190500305901