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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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