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PMID: 8562938 Published · ppublish English Clinical Trial Comparative Study Journal Article Multicenter Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23.

Blood ·Vol. 87 ·No. 3 ·1996-02-01 ·Pages 1123-33

Smith FO, Rauch C, Williams DE, March CJ, Arthur D, Hilden J, Lampkin BC, Buckley JD, Buckley CV, Woods WG, Dinndorf PA, Sorensen P, Kersey J, Hammond D, Bernstein ID

Abstract

In our efforts to produce monoclonal antibodies that recognize cell-surface antigens expressed by hematopoietic precursor and stromal cells, we generated a monoclonal antibody, 7.1, which recognizes a 220- to 240-kD cell-surface protein whose N-terminal amino acid sequence is identical to the rat NG2 chondroitin sulfate proteoglycan molecule. This chondroitin sulfate proteoglycan, previously reported to be expressed by human melanoma cells, was not found to be expressed by normal hematopoietic cells, nor was it expressed on the cell surface of cell lines of hematopoietic origin including cell lines with 11q23 abnormalities. It was found on the cell surface of acute myeloid leukemia (AML) blasts and cell lines derived from nonhematopoietic tissues. Samples of leukemic marrow from 166 children with AML enrolled on Childrens Cancer Group protocol 213 were evaluated for cell-surface expression of this proteoglycan molecule. In 18 of 166 (11%) patient samples, greater than 25% of leukemic blasts expressed the NG2 molecule. These 18 patients had a poorer outcome with respect to survival (P = .002) and event-free survival (P = .035) with an actuarial survival at 4 years of 16.7%. Blast cell expression of the NG2 molecule was strongly associated with French-American-British M5 morphology (P < .0001) and abnormalities in chromosome band 11q23, site of the MLL gene. These results show that the NG2 molecule is expressed by malignant hematopoietic cells that have abnormalities in chromosome band 11q23, suggesting that antibody 7.1 may be useful in the rapid identification of this group of poor-prognosis patients.

MeSH Terms
Actuarial Analysis Acute Disease Adolescent Amino Acid Sequence Aneuploidy Animals Antibodies, Monoclonal/immunology Antigens/biosynthesis,genetics,immunology Antigens, Neoplasm/biosynthesis,genetics,immunology Biomarkers, Tumor/analysis Bone Marrow/pathology Cell Line, Transformed Child Child, Preschool Chromosome Aberrations Chromosomes, Human, Pair 11/ultrastructure DNA-Binding Proteins/genetics Female HeLa Cells/chemistry Hematopoietic Stem Cells/metabolism Histone-Lysine N-Methyltransferase Humans Leukemia, Monocytic, Acute/genetics,metabolism,mortality,pathology Leukemia, Myeloid/genetics,metabolism,mortality,pathology Leukemia, Myelomonocytic, Acute/genetics,metabolism,mortality,pathology Male Mice Mice, Inbred BALB C Molecular Sequence Data Myeloid-Lymphoid Leukemia Protein Neoplastic Stem Cells/metabolism Prognosis Proteoglycans/biosynthesis,genetics,immunology Proto-Oncogenes Rats Survival Rate Transcription Factors Treatment Outcome Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Antigens Antigens, Neoplasm Biomarkers, Tumor DNA-Binding Proteins KMT2A protein, human Proteoglycans Transcription Factors chondroitin sulfate proteoglycan 4 Myeloid-Lymphoid Leukemia Protein Histone-Lysine N-Methyltransferase Kmt2a protein, mouse
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Smith F O
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rauch C
Williams D E
March C J
Arthur D
Hilden J
Lampkin B C
Buckley J D
Buckley C V
Woods W G
Dinndorf P A
Sorensen P
Kersey J
Hammond D
Bernstein I D
Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
Published
1996-02-01
Pages
1123-33
Language
English
Region
United States
NLM ID
7603509
Subset
IM
Grants
NCI NIH HHS · CA 13539 · United States
NCI NIH HHS · CA39492 · United States
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