ORIGINAL ARTICLE: CLINICAL Expression level of lipoprotein lipase and dystrophin genes predict survival in B-cell chronic lymphocytic leukemia E. A. NIKITIN 1 , S. G. MALAKHO 2 , B. V. BIDERMAN 1 , A. V. BARANOVA 3,4 , Y. Y. LORIE 1 , A. Y. SHEVELEV 5 , M. M. PEKLO 5 , T. N. VLASIK 5 , E. A. MOSKALEV 1 , B. V. ZINGERMAN 1 , I. A. VOROB’EV 1 , A. B. POLTARAUS 2 , A. B. SUDARIKOV 1 , & A. I. VOROBJEV 1 1 Hematology Research Center of Russia, Moscow, Russia, 2 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia, 3 Molecular and Microbiology Department, College of Science, George Mason University, Fairfax, VA, USA, 4 Russian Center of Medical Genetics, Moscow, Russia, and 5 Russian Cardiology Research and Production Center, Moscow, Russia (Received 30 October 2006; revised 23 December 2006; accepted 24 January 2007) Abstract Mutational status of immunoglobulin variable region genes (VH-genes) is known as the strongest predictor of long term prognosis in B-CLL. However, applications in the routine clinical practice are time consuming, and therefore some other predictions are required. In this study, we have compared prognostic values of real time PCR quantification of the expression levels of four genes previously shown to be differentially expressed in V H -unmutated and mutated B-CLL subtypes: ZAP-70, ZBTB20, DMD and LPL. The study included 134 B-CLL patients. Expression levels of LPL and DMD genes were significantly correlated to mutational status, while expression levels of of ZAP-70 gene correlated only in CD19þ selected cases (N ¼ 40). No correlation was observed for ZBTB20 gene. Expression levels of LPL and DMD predicted overall survival in the entire cohort of patients. Prognostic values of LPL gene expression levels were significant even for CLL patients with stage A. Quantitative RT-PCR assays for measuring LPL gene expression are robust enough to be introduced into routine clinical practice. Keywords: Lipoprotein lipase, B-cell chronic lymphocytic leukemia, dystrophin, ZAP-70, IgV H gene mutational status, Q-RT-PCR Introduction B-cell chronic lymphocytic leukemia is a disease with a highly heterogeneous clinical course. Some patients have rapidly progressive clinical course and even- tually die from B-CLL or its complications, whereas others survive for many years without any treatment. Overall survival varies from several months to 20 and more years. With the appearance of effective novel treatment modalities such as monoclonal antibodies and purine analogues, traditionally palliative ap- proach to B-CLL is being gradually replaced by a risk adapted therapy [1]. Risk adapted approach implies early identification of prognostic factors allowing tailored clinical decisions. Therefore, search for the novel prognostic factors followed by precise determination of their relative value as compared to other predictors is increasingly important. Many prognostic factors have been identified in B-CLL, including clinical, morphological, cytoge- netic, molecular and serological parameters [2]. In the late 1990s, it was shown that B-CLL may be divided into two prognostic groups depending on whether the variable region of the immunoglobulin heavy-chain locus has undergone somatic hypermu- tation or not [3 – 5]. Patients with unmutated V H genes follow more progressive disease course than those with somatic mutations. In contrast to many Correspondence: Dr. Eugene Nikitin, Hematology Research Center of Russia, Laboratory of Molecular Hematology, Novozykovski pr. 4a, Moscow, Russia, 125167. Tel: þ495-612-65-11. Fax: þ495-612-42-52. E-mail: eugene_nikitin@mail.ru Leukemia & Lymphoma, May 2007; 48(5): 912 – 922 ISSN 1042-8194 print/ISSN 1029-2403 online Ó 2007 Informa UK Ltd. DOI: 10.1080/10428190701245112 Leuk Lymphoma Downloaded from informahealthcare.com by Universitaetsbibliothek Erlangen-Nuernberg on 05/28/14 For personal use only.