CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells.
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.
Laboratory of Experimental Immunology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System, 350 Community Drive, Manhasset, NY 11030, USA.
Rajendra N
RN
Damle
Sonal
S
Temburni
Carlo
C
Calissano
Sophia
S
Yancopoulos
Taraneh
T
Banapour
Cristina
C
Sison
Steven L
SL
Allen
Kanti R
KR
Rai
Nicholas
N
Chiorazzi
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology*; D018956:CD5 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000473:pathology*; D008875:Middle Aged; D019098:Telomerase / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D000954:Antigens, Surface; D018956:CD5 Antigens; D019394:Ki-67 Antigen; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019098:Telomerase; D051997:ADP-ribosyl Cyclase 1