Chlorambucil drug resistance in chronic lymphocytic leukemia: the emerging role of DNA repair.
نویسندگان
چکیده
Various mechanisms have been implicated in nitrogen mustard drug resistance. The role of these mechanisms in the development of chlorambucil drug resistance in chronic lymphocytic leukemia (CLL) is discussed. We review these mechanisms with emphasis on the emerging role of DNA repair, and specifically, recombinational repair. Inhibition of these repair processes may lead to new therapies, not only in CLL, but in other malignancies as well.
منابع مشابه
RAPID COMMUNICATION DNA-Dependent Protein Kinase Activity Correlates With Clinical and In Vitro Sensitivity of Chronic Lymphocytic Leukemia Lymphocytes to Nitrogen Mustards
The objective of this study is to investigate the role of DNA-dependent protein kinase (DNA-PK) in the chronic lymphocytic leukemia (CLL) lymphocyte response to nitrogen mustard therapy. DNA-PK is a nuclear serine/threonine kinase that functions in DNA double-strand break repair and in the joining process in recombination mechanisms. In a series of 34 patients with B-CLL, either untreated (n 5 ...
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The objective of this study is to investigate the role of DNA-dependent protein kinase (DNA-PK) in the chronic lymphocytic leukemia (CLL) lymphocyte response to nitrogen mustard therapy. DNA-PK is a nuclear serine/threonine kinase that functions in DNA double-strand break repair and in the joining process in recombination mechanisms. In a series of 34 patients with B-CLL, either untreated (n = ...
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Our previous studies with B-cell chronic lymphocytic leukemia (B-CLL) have suggested that one of the mechanisms of nitrogen mustard (NM) drug resistance is increased repair of drug-induced damage. We have postulated that recombination may play a crucial role in this process. The human homologue of Rad51, (HsRad51), has homology to the RecA protein in Escherichia coli, which is implicated in rec...
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The time course of the formation and persistence of repair-induced DNA lesions such as single-strand breaks (SSBs) were determined in isolated lymphocytes derived from 32 patients with chronic lymphocytic leukemia (CLL) using the single-cell gel electrophoresis (SCGE, "comet") assay. After pulse-exposure to N-ethyl-N-nitrosourea (EtNU), the initial amount of SSBs (t0 SCGE values) and the time p...
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Chlorambucil (CLB) uptake by chronic lymphocytic leukemia lymphocytes was studied using a radiometric and a newly developed high-performance liquid chromatography assay. CLB labeled with 14C in either the chloroethyl group or phenyl ring was used with identical results. Drug accumulation by the cells was found to peak at 30 s, was independent of temperature, and was proportional to medium CLB c...
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عنوان ژورنال:
- Clinical cancer research : an official journal of the American Association for Cancer Research
دوره 7 3 شماره
صفحات -
تاریخ انتشار 2001