Document Detail

Combined use of nonmyelosuppressive nitrosourea analogues with hydroxyurea in the induction of F-cell production in a human erythroleukemic cell line.
MedLine Citation:
PMID:  12842704     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Although hydroxyurea (HU) has been used clinically to treat patients with sickle cell disease (SCD), not all patients benefit from HU treatment due to its toxicity. The objective of this study was to investigate the effectiveness of the use of two new Hb F-inducing nitrosourea analogues, 2-[3-(2-methyl, 2-nitroso) ureido]-2-deoxy-D-glucopyranose (MNGU) and 2-[3-(2-chloroethyl) ureido]-2-deoxy-D-glucopyranose (CGU), in combination with HU in K562 cells or erythroid progenitors. MATERIALS AND METHODS: After K562 cells were cultured with different concentrations of HU with CGU or MNGU, aliquots of the cells were obtained to determine the total (benzidine-positive) hemoglobin level, number of F cells, and Hb F level. Erythroid progenitor cells of SCD patients and healthy donors were cultured with the optimal drug concentrations, and the number of BFU-E and Hb F level were determined. RESULTS: Our results showed that the combined use of HU with CGU or MNGU increased the number of both benzidine-positive normoblasts and F cells in a synergistic manner. Further, a lower concentration of HU was required to induce a significant level of Hb F synthesis when combined with either of the two compounds in comparison with treatment with HU alone. On day 4, the number of benzidine-positive cells was 4.5- to 6.5-fold and the number of F cells was 5.0- to 8.0-fold higher than the respective numbers in the untreated K562 cells. Similarly, a 3.2- to 14.3-fold induction of Hb F was obtained when human erythroid progenitors from SCD patients were treated with the same drug combinations. CONCLUSION: Based on these results, the use of CGU or MNGU in combination with HU might offer substantial benefits to patients with SCD and other hemoglobinopathies.
Efemwonkiekie W Iyamu; Samuel E Adunyah; Hugo Fasold; Kazumi Horiuchi; Surendra Baliga; Kwaku Ohene-Frempong; Ernest A Turner; Toshio Asakura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental hematology     Volume:  31     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-04     Completed Date:  2003-08-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  592-600     Citation Subset:  IM    
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA.
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MeSH Terms
Cell Division / drug effects
Fetal Hemoglobin / biosynthesis*
Hydroxyurea / pharmacology*
K562 Cells
Leukemia, Erythroblastic, Acute / metabolism*,  pathology
Monosaccharides / pharmacology*
Urea / analogs & derivatives,  pharmacology*
Grant Support
2P60 H13832//PHS HHS; U24 HL 58930/HL/NHLBI NIH HHS
Reg. No./Substance:
0/2-(3-(2-chloroethyl) ureido)-2-deoxy-D-glucopyranose; 0/2-(3-(2-methyl, 2-nitroso) ureido)-2-deoxy-D-glucopyranose; 0/Monosaccharides; 127-07-1/Hydroxyurea; 57-13-6/Urea; 9034-63-3/Fetal Hemoglobin

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