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.
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.
Smith
F O
FO
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rauch
C
C
Williams
D E
DE
March
C J
CJ
Arthur
D
D
Hilden
J
J
Lampkin
B C
BC
Buckley
J D
JD
Buckley
C V
CV
Woods
W G
WG
Dinndorf
P A
PA
Sorensen
P
P
Kersey
J
J
Hammond
D
D
Bernstein
I D
ID
D000206:Actuarial Analysis; D000208:Acute Disease; D000293:Adolescent; D000595:Amino Acid Sequence; D000782:Aneuploidy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001853:Bone Marrow / Q000473:pathology; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006367:HeLa Cells / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011519:Proto-Oncogenes; D051381:Rats; D015996:Survival Rate; D014157:Transcription Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D000099216:Chondroitin Sulfate Proteoglycan 4
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D011509:Proteoglycans; D014157:Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C497422:KMT2A protein, human; C497423:Kmt2a protein, mouse