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.
Subject(s)
Antigens, Neoplasm/biosynthesis , Antigens/biosynthesis , Biomarkers, Tumor/analysis , Chromosomes, Human, Pair 11/ultrastructure , Hematopoietic Stem Cells/metabolism , Leukemia, Myeloid/metabolism , Neoplastic Stem Cells/metabolism , Proteoglycans/biosynthesis , Proto-Oncogenes , Transcription Factors , Actuarial Analysis , Acute Disease , Adolescent , Amino Acid Sequence , Aneuploidy , Animals , Antibodies, Monoclonal/immunology , Antigens/genetics , Antigens/immunology , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Bone Marrow/pathology , Cell Line, Transformed , Child , Child, Preschool , Chromosome Aberrations , DNA-Binding Proteins/genetics , Female , HeLa Cells/chemistry , Histone-Lysine N-Methyltransferase , Humans , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/metabolism , Leukemia, Monocytic, Acute/mortality , Leukemia, Monocytic, Acute/pathology , Leukemia, Myeloid/genetics , Leukemia, Myeloid/mortality , Leukemia, Myeloid/pathology , Leukemia, Myelomonocytic, Acute/genetics , Leukemia, Myelomonocytic, Acute/metabolism , Leukemia, Myelomonocytic, Acute/mortality , Leukemia, Myelomonocytic, Acute/pathology , Male , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Myeloid-Lymphoid Leukemia Protein , Prognosis , Proteoglycans/genetics , Proteoglycans/immunology , Rats , Survival Rate , Treatment Outcome , Tumor Cells, CulturedABSTRACT
The prognostic significance of c-kit receptor expression on leukemic blast cells was determined in 122 children with acute myeloid leukemia (AML) entered onto Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as well as outcome were analyzed according to the percentage of blast cells expressing c-kit receptors and the relative number of c-kit receptors per cell as determined by indirect immunofluorescence. c-kit receptor expression was strongly associated with the expression of the CD34 antigen. However, contrary to findings in adult patients with AML, c-kit receptor expression by childhood AML blast cells was not predictive of a poor response to therapy.
