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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3352-3359.
Prepublished online as a Blood First Edition Paper on August 7, 2007; DOI 10.1182/blood-2007-04-083832.
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Submitted April 4, 2007
Accepted July 26, 2007
CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells
Rajendra N Damle, Sonal Temburni, Carlo Calissano, Sophia Yancopoulos, Taraneh Banapour, Cristina Sison, Steven L. Allen, Kanti R. Rai, and Nicholas Chiorazzi*
Department of Medicine, New York University School of Medicine, New York, NY, United States
Laboratory of Experimental Immunology, The Feinstein Institute for Medical Research, North Shore - LIJ Health System, Manhasset, NY, United States
Department of Biostatistics, The Feinstein Institute for Medical Research, North Shore - LIJ Health System, Manhasset, New York, United States
Monter Cancer Center, North Shore - LIJ Health System, Lake Success, New York, United States
Division of Hematology/Oncology, Long Island Jewish Medical Center, North Shore - LIJ Health System, Lake Success, NY, United States
Depts of Cell Biology & Medicine, Albert Einstein College of Medicine, Manhasset, NY, United States
* Corresponding author; email: nchizzi{at}nshs.edu.
CLL cells are thought to have diminished cell cycling capacity, a view challenged by their phenotypic resemblance to activated human B lymphocytes. The present study addresses the cell cycling status of CLL cells, focusing on those leukemic cells expressing CD38, a molecule involved in signaling and activation that also serves as a prognostic marker in this disease. CD38+ and CD38- members of individual CLL clones were analyzed for co-expression of molecules associated with cellular activation (CD27, CD62L and CD69), cell cycle entry (Ki-67), signaling (ZAP-70), and protection from apoptosis (telomerase and Bcl-2). Regardless of the size of the CD38+ fraction within a CLL clone, CD38+ subclones are markedly enriched for expression of Ki-67, CD27, CD62L, CD69, ZAP-70, human telomerase reverse transcriptase, and telomerase activity. Although the percentage of cells (~2%) entering the cell cycle, as defined by Ki-67 expression, is small, the absolute number within a clone can be sizeable and is contained primarily within the CD38+ fraction. Despite these activation/proliferation differences, both CD38+ and CD38- fractions have similar telomere lengths suggesting that CD38 expression is dynamic and transient. These findings may help explain why high percentages of CD38+ cells within clones are associated with poor clinical outcome.
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