Format

Send to

Choose Destination
Leukemia. 2017 Jun;31(6):1340-1347. doi: 10.1038/leu.2017.11. Epub 2017 Jan 11.

Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood.

Author information

1
Hematology Branch, National, Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
2
Department of Medicine, Uniformed Services University, Bethesda, MD.
3
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
4
KineMed Inc., Emeryville, CA.
5
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
6
Department of Pharmacy, National Institutes of Health Clinical Center, Bethesda, MD.
7
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
8
Departments of Medicine and Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY.
#
Contributed equally

Abstract

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 (2H) in vivo labeling method in which patients consumed deuterated (heavy) water (2H2O), 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 CXCR4dimCD5bright 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.

PMID:
28074063
PMCID:
PMC5462849
[Available on 2017-07-11]
DOI:
10.1038/leu.2017.11
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center