title: Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(-)/CD24(-)/CD65s(+)/CD15(+) B-cell phenotype.
abstract: The expression of the chondroitin sulfate proteoglycan neuron-glial antigen 2 (NG2) has been demonstrated in association with rearrangement of the mixed lineage leukemia (MLL) gene in acute leukemia, but the frequency of NG2 expression in adult acute lymphoblastic leukemia (ALL) is yet unknown. We evaluated NG2 expression in 313 adult ALL patients by flow cytometry and simultaneously determined MLL rearrangement in 120 adult patients out of them with B-precursor ALL by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. A total of 57% of pro-B ALL, 2% of common ALL and 20% of pre-B ALL were NG2 positive, but NG2 was absent in T-ALL and mature B-ALL. In B-precursor ALL, NG2 expression was significantly associated with a CD10(-)/CD34(-)/CD24(-)/CD65s(+)/CD15(+)/CD13(-)/CD33(-) phenotype and showed a sensitivity, specificity and positive predictive value of 0.89, 0.89, and 0.93 for MLL rearrangement, respectively. NG2 was positive in three patients without detectable MLL rearrangement and negative in eight patients with MLL-AF4 transcripts. However, NG2 predicted with a 100% accuracy MLL rearrangement among patients disclosing a CD65s(+) and/or CD15(+) immunophenotype. In summary, NG2 adds to a more precise identification of high-risk adult ALL and should therefore be included into diagnostic marker panels. As NG2 is negative in non-malignant hematopoietic cells, this novel antigen might also serve in future studies as a powerful marker in monitoring minimal residual disease.
authors.affiliation: Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Klinikum Benjamin Franklin, Freie Universität, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: H
authors.initials: H
authors.lastname: Rieder
authors.forename: B
authors.initials: B
authors.lastname: Schläger
authors.forename: T
authors.initials: T
authors.lastname: Burmeister
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: E
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000941:Antigens / Q000032:analysis*; D015703:Antigens, CD / Q000032:analysis*; D001402:B-Lymphocytes / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017385:Sequence Homology; D014157:Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D015703:Antigens, CD; D015415:Biomarkers; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D011509:Proteoglycans; D012333:RNA, Messenger; D014157:Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C497422:KMT2A protein, human; C113855:MLL-AF4 fusion protein, human