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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-09-2906.

Submitted September 23, 2002
Accepted February 3, 2003
High Expression of Activation-Induced Cytidine Deaminase (AID) and Splice Variants is a Distinctive Feature of Poor Prognosis Chronic Lymphocytic Leukemia
Helen McCarthy, William G Wierda, Lynn L Barron, Candy C Cromwell, Jing Wang, Kevin R Coombes, Roberto Rangel, Kojo S Elenitoba-Johnson, Michael J Keating, and Lynne V Abruzzo*
Leukemia, UT M.D. Anderson Cancer Center, Houston, TX, USA
Hematopathology, UT M.D. Anderson Cancer Center, Houston, TX, USA
Biostatistics, UT M.D. Anderson Cancer Center, Houston, TX, USA
Immunology, UT M.D. Anderson Cancer Center, Houston, TX, USA
Anatomic Pathology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
* Corresponding author; email: labruzzo{at}mdanderson.org.
In chronic lymphocytic leukemia (CLL), analysis of immunoglobulin heavy chain variable regions for somatic hypermutation identifies two prognostic subsets, mutated and unmutated. Investigators have postulated that unmutated and mutated CLL arises from malignant transformation of pre- and post-germinal center (GC) B-cells, respectively. Alternatively, unmutated cases may arise from B-cells stimulated by T-cell independent antigens or from GC B-cells with inactive somatic hypermutation. Activation-induced cytidine deaminase (AID), a protein essential for somatic hypermutation, is expressed GC B-cells where this process occurs. We investigated AID mRNA expression in 20 CLL cases. In eight cases we detected high expression of wild-type AID mRNA and two splice variants; in 12 cases and five normal peripheral blood B-cell samples we detected no expression using standard conditions. Seven of eight CLL cases that highly expressed AID were unmutated, suggesting that this subset may arise from GC-experienced B-cells with inactive somatic hypermutation, and may predict prognosis.

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