In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 24 ( 2008-12-15), p. 10137-10144
Abstract:
Although accumulating evidence indicates that chronic lymphocytic leukemia (CLL) is a disease with appreciable cell dynamics, it remains uncertain whether this also applies to patients with stable disease. In this study, 2H2O was administered to a clinically homogeneous cohort of nine stable, untreated CLL patients. CLL dynamics in blood and bone marrow were determined and compared with normal B-cell dynamics in blood from five healthy individuals who underwent a similar 2H2O labeling protocol. Average CLL turnover rates (0.08–0.35% of the clone per day) were ∼2-fold lower than average B-cell turnover rates from healthy individuals (0.34–0.89%), whereas the rate at which labeled CLL cells in blood disappeared (0.00–0.39% of B cells per day) was ∼10-fold lower compared with labeled B cells from healthy individuals (1.57–4.24% per day). Leukemic cell turnover variables inversely correlated with the level of somatic hypermutation of the CLL clone (IgVH mutations). Although CLL cells in bone marrow had a higher level of label enrichment than CLL cells in blood, no difference between proliferation rates and proapoptotic and antiapoptotic profiles of CLL cells from these compartments was observed. These data suggest that, in stable disease, there is a biological relationship between the degree of somatic hypermutation of the CLL clone and its dynamics in vivo. Furthermore, in contrast to lymph nodes, the bone marrow does not seem to be a major CLL proliferation site. [Cancer Res 2008;68(24):10137–44]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-08-2325
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2008
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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