Abstract
CD38, a surface protein whose expression increases upon normal B-cell activation, is a marker of disease aggression in B-cell chronic lymphocytic leukemia (B-CLL). Higher percentages of CD38-expressing CLL B cells may be found in lymphoid compartments compared to peripheral blood. Therefore, it is possible that although CLL B cells are resting, CD38 may be a marker of recent cell activation prior to entry into the periphery. To address this hypothesis, we examined the association of CD38 expression with other activation antigens identified in gene expression profiling experiments and include CD18, CD49d, CD20, and subunit 5 of the anaphase-promoting complex/cyclosome. We found that all these markers were more highly expressed in leukemic B cells from CD38-positive CLL patients. Lastly, because interferon is known to modulate CD38 expression, we used IFN-α to test the ability of CLL B cells to increase CD38 expression in vitro. Interestingly, IFN stimulation only modulated CD38 expression in CLL B cells that already expressed CD38. Taken together, these data suggest that CD38 is a marker of a more recently activated CLL B cell. This in turn may explain the biological and clinical differences between CD38-positive type B-CLL and CD38-negative type B-CLL.
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Acknowledgements
We thank Bonnie Arendt, Nancy Bone, Cheryl Jankiewicz, and Renee Tschumper for their technical assistance, Dr Karla Ballman and Bruce Morlan for their assistance in analyzing the exploratory gene expression study data, and Dr Clive Zent for his insightful comments. This study was supported by the National Institutes of Health Training Grant T32-HL67742 (BTP), R01 CA91942 (NEK), and generous philanthropic support provided by Mr Edson Spencer.
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Pittner, B., Shanafelt, T., Kay, N. et al. CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation. Leukemia 19, 2264–2272 (2005). https://doi.org/10.1038/sj.leu.2403975
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DOI: https://doi.org/10.1038/sj.leu.2403975
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