High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia.

作者: D Heintel , E Kroemer , D Kienle , I Schwarzinger , A Gleiss

DOI: 10.1038/SJ.LEU.2403294

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摘要: Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells 80 patients with B-CLL. was detected 45 (56%) at various levels, but undetectable 35 (44%). PCR positivity associated unmutated IGVH gene status (22 25 patients; P=0.002) and unfavourable cytogenetics (18 23 deletion 11q or loss p53; P=0.040). Using a threshold level 0.01-fold compared to Ramos control cells, even more significant associations were observed (P=0.001 IGVH; P=0.002 cytogenetics). A correlation between individual levels percentage VH homology (R=0.41; P=0.001). predicted an odds ratio 8.31 (P=0.003) poor risk 3.46 (P=0.032). Significance retained after adjustment Binet Rai stages. stable over time. These data suggest potential role as prognostic marker

参考文章(34)
Bertold Emmerich, Dagmar Adorf, Christoph Nerl, Michael Hallek, Raymonde Busch, Wolfgang Knauf, Eckhard Thiel, Ingrid Kuhn-Hallek, Marianne Ostwald, Irmgard Langenmayer, Hermann Dietzfelbinger, Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood. ,vol. 93, pp. 1732- 1737 ,(1999) , 10.1182/BLOOD.V93.5.1732
KR Rai, A Sawitsky, EP Cronkite, AD Chanana, RN Levy, BS Pasternack, Clinical staging of chronic lymphocytic leukemia. Blood. ,vol. 46, pp. 219- 234 ,(1975) , 10.1182/BLOOD.V46.2.219.219
Stuart M. Lichtman, Philip Schulman, Vincent P. Vinciguerra, Kanti R. Rai, Manlio Ferrarini, Nicholas Chiorazzi, Rajendra N. Damle, Tarun Wasil, Franco Fais, Fabio Ghiotto, Angelo Valetto, Steven L. Allen, Aby Buchbinder, Daniel Budman, Klaus Dittmar, Jonathan Kolitz, Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. ,vol. 94, pp. 1840- 1847 ,(1999) , 10.1182/BLOOD.V94.6.1840
Terry J. Hamblin, Zadie Davis, Anne Gardiner, David G. Oscier, Freda K. Stevenson, Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. ,vol. 94, pp. 1848- 1854 ,(1999) , 10.1182/BLOOD.V94.6.1848
Alexander Kröber, Till Seiler, Axel Benner, Lars Bullinger, Elsbeth Brückle, Peter Lichter, Hartmut Döhner, Stephan Stilgenbauer, VH mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia Blood. ,vol. 100, pp. 1410- 1416 ,(2002) , 10.1182/BLOOD.V100.4.1410.H81602001410_1410_1416
David G. Oscier, Anne C. Gardiner, Sarah J. Mould, Sharron Glide, Zadie A. Davis, Rachel E. Ibbotson, Martin M. Corcoran, Robert M. Chapman, Peter W. Thomas, J. Adrian Copplestone, Jenny A. Orchard, Terry J. Hamblin, Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood. ,vol. 100, pp. 1177- 1184 ,(2002) , 10.1182/BLOOD.V100.4.1177.H81602001177_1177_1184
W Reinisch, M Willheim, M Hilgarth, C Gasché, R Mader, S Szepfalusi, G Steger, R Berger, K Lechner, G Boltz-Nitulescu, Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia. Journal of Clinical Oncology. ,vol. 12, pp. 2146- 2152 ,(1994) , 10.1200/JCO.1994.12.10.2146
J. L. Binet, M. Leporrier, G. Dighiero, D. Charron, G. Vaugier, H. Merle Beral, J. C. Natali, M. Raphael, B. Nizet, J. Y. Follezou, A clinical staging system for chronic lymphocytic leukemia.Prognostic significance Cancer. ,vol. 40, pp. 855- 864 ,(1977) , 10.1002/1097-0142(197708)40:2<855::AID-CNCR2820400239>3.0.CO;2-1
Heinz Jacobs, Linda Bross, Towards an understanding of somatic hypermutation. Current Opinion in Immunology. ,vol. 13, pp. 208- 218 ,(2001) , 10.1016/S0952-7915(00)00206-5
Ulf Thunberg, Anna Johnson, Göran Roos, Ingrid Thörn, Gerard Tobin, Jan Sällström, Christer Sundström, Richard Rosenquist, None, CD38 expression is a poor predictor for VH gene mutational status and prognosis in chronic lymphocytic leukemia. Blood. ,vol. 97, pp. 1892- 1894 ,(2001) , 10.1182/BLOOD.V97.6.1892