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, (2)H(2)O 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 (2)H(2)O labeling protocol. Average CLL turnover rates (0.08-0.35% of the clone per day) were approximately 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 approximately 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
van Gent R,Kater AP,Otto SA,Jaspers A,Borghans JA,Vrisekoop N,Ackermans MA,Ruiter AF,Wittebol S,Eldering E,van Oers MH,Tesselaar K,Kersten MJ,Miedema Fdoi
10.1158/0008-5472.CAN-08-2325subject
Has Abstractpub_date
2008-12-15 00:00:00pages
10137-44issue
24eissn
0008-5472issn
1538-7445pii
68/24/10137journal_volume
68pub_type
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