Document Detail


Normal and leukemic hematopoietic cells manifest differential sensitivity to inhibitory effects of c-myb antisense oligodeoxynucleotides: an in vitro study relevant to bone marrow purging.
MedLine Citation:
PMID:  2006173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The c-myb protooncogene is preferentially expressed in hematopoietic cells, and its encoded protein, Myb, is required for hematopoietic cell proliferation. To analyze the relative Myb dependence of normal and leukemic human hematopoietic progenitor cells, normal bone marrow cells, several types of leukemic blast cells, and 1:1 mixtures of normal and leukemic cells were cultured in the presence of c-myb sense or antisense oligodeoxynucleotides; cell viability and cloning efficiency were then assessed. c-myb sense oligomers had negligible effects on normal and leukemic cells. In contrast, c-myb antisense oligomers strongly inhibited or completely abolished clonogenic growth of a T-cell leukemia line, 78% (18 of 23) of primary acute myelogenous leukemia cases examined, and 4 of 5 primary chronic myelogenous leukemia (CML) cases in blast crisis. In three of the latter patients, polymerase chain reaction analysis of a 1:1 mixture of c-myb antisense-treated normal and CML cells revealed a complete absence of bcr-abl expression, suggesting that the CML clonogenic units had been completely eliminated from the cultures. At antisense doses that inhibited leukemic cell growth, normal hematopoietic progenitor cells survived. Thus, normal and leukemic hematopoietic cells show differential sensitivity to the toxic effects of c-myb antisense DNA. Perturbation of c-myb function with antisense oligodeoxynucleotides might eventually form the basis for a molecular approach to leukemia therapy, perhaps most immediately as ex vivo bone marrow purging agents.
Authors:
B Calabretta; R B Sims; M Valtieri; D Caracciolo; C Szczylik; D Venturelli; M Ratajczak; M Beran; A M Gewirtz
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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:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  88     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1991 Mar 
Date Detail:
Created Date:  1991-04-25     Completed Date:  1991-04-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2351-5     Citation Subset:  IM    
Affiliation:
Department of Pathology, Temple University School of Medicine, Philadelphia, PA 19140.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Blast Crisis / pathology
Bone Marrow / pathology
Bone Marrow Cells*
Cell Line
Hematopoietic Stem Cells / cytology*,  drug effects,  pathology
Humans
Leukemia
Leukemia, Myeloid, Acute / pathology*
Lymphocyte Depletion*
Molecular Sequence Data
Oligonucleotides, Antisense / chemical synthesis,  pharmacology*
Oncogenes*
Grant Support
ID/Acronym/Agency:
CA01324/CA/NCI NIH HHS; CA36896/CA/NCI NIH HHS; CA46782/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oligonucleotides, Antisense
Comments/Corrections

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