期刊
LEUKEMIA
卷 31, 期 6, 页码 1340-1347出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2017.11
关键词
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资金
- Intramural Research Program of the National, Heart, Lung and Blood Institute
- National Cancer Institute, the National Institutes of Health
- RO1 grant from the National Cancer Institute, NIH
- Danish Cancer Society
- National Cancer Institute
- RO1 grant from the NIH National Cancer Institute [CA081554]
- Novo Nordisk Fonden [NNF16OC0019302] Funding Source: researchfish
- The Danish Cancer Society [R72-A4347] Funding Source: researchfish
Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide (H-2) in vivo labeling method in which patients consumed deuterated (heavy) water ((H2O)-H-2), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4(dim)CD5(bright) phenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.
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