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

被引:131
作者
Damle, Rajendra N.
Tembumi, Sonal
Calissano, Carlo
Yancopoulos, Sophia
Banapour, Taraneh
Sison, Cristina
Allen, Steven L.
Rai, Kanti R.
Chiorazzi, Nicholas
机构
[1] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Expt Immunol Lab, Manhasset, NY 11030 USA
[2] NYU, Sch Med, Dept Med, New York, NY USA
[3] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Dept Biostat, Manhasset, NY 11030 USA
[4] N Shore LIJ Hlth Syst, Monter Canc Ctr, Lake Success, NY USA
[5] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA
[6] N Shore LIJ Hlth Syst, Div Hematol & Oncol, Lake Success, NY USA
[7] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA
[8] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA
关键词
D O I
10.1182/blood-2007-04-083832
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:3352 / 3359
页数:8
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