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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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NEOPLASIA

CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells

Rajendra N. Damle1,2, Sonal Temburni1, Carlo Calissano1, Sophia Yancopoulos1, Taraneh Banapour1, Cristina Sison3, Steven L. Allen4,5, Kanti R. Rai5,6, and Nicholas Chiorazzi1,7

1 Laboratory of Experimental Immunology, The Feinstein Institute for Medical Research, North Shore–Long Island Jewish (LIJ) Health System, Manhasset, NY; 2 Department of Medicine, New York University School of Medicine, New York, NY; 3 Department of Biostatistics, The Feinstein Institute for Medical Research, North Shore–LIJ Health System, Manhasset, NY; 4 Monter Cancer Center, North Shore–LIJ Health System, Lake Success, NY; 5 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 6 Division of Hematology and Oncology, North Shore–LIJ Health System, Lake Success, NY; 7 Departments of Cell Biology and Medicine, Albert Einstein College of Medicine, Bronx, NY

Chronic lymphocytic leukemia (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 coexpression 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, ZAP-70, human telomerase reverse transcriptase, and telomerase activity. Although the percentage of cells (approximately 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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