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

2007; Elsevier BV; Volume: 110; Issue: 9 Linguagem: Inglês

10.1182/blood-2007-04-083832

1528-0020

Rajendra N. Damle, Sonal Temburni, Carlo Calissano, Sophia Yancopoulos, Taraneh Banapour, Cristina Sison, Steven L. Allen, R. Kanti, Nicholas Chiorazzi,

Advanced Breast Cancer Therapies

Abstract 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.