Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements

Blood. 1996 Feb 1;87(3):1134-9.

Abstract

Monoclonal antibody 7.1, which recognizes the chondroitin sulfate proteoglycan molecule NG2, was used to screen prospectively blast cells from 104 consecutive children at initial presentation with acute lymphoblastic leukemia (ALL). Reactivity with this antibody was found in 9 cases (8.6%), of whom 5 had a t(4;11)(q21;q23) and 4 had a t(11;19)(p13;q23). None of the NG2- cases had either translocation. Southern blot analysis disclosed MLL gene rearrangement in only the 9 cases with 7.1 reactivity plus the t(4;11)(q21;q23) or t(11;19)(q23;p13) translocation. MLL gene rearrangements were not detected in 89 patient leukemic samples that did not express NG2, including 7 patients with del(11)(q23) or inv(11)(p13q23). As expected from the association with t(4;11) and t(11;19), NG2+ cases were significantly more likely to be infants, to have hyperleukocytosis and central nervous system involvement, to be CD10-, and to express myeloid-associated antigens CD15 and CD65. Despite short follow-up duration, 3 of the NG2+ cases have relapsed while the other 101 patients remain in remission. Thus, blast cell surface expression of NG2 is useful for identifying patients with ALL having t(4;11) or t(11;19) translocations that are associated with poor prognosis, especially in the infant age group.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens / analysis*
  • Antigens / genetics
  • Antigens / immunology
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 11 / ultrastructure*
  • Chromosomes, Human, Pair 19 / ultrastructure
  • Chromosomes, Human, Pair 4 / ultrastructure
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Male
  • Mice
  • Myeloid-Lymphoid Leukemia Protein
  • Neoplastic Stem Cells / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proteoglycans / analysis*
  • Proteoglycans / genetics
  • Proteoglycans / immunology
  • Proto-Oncogenes*
  • Rats
  • Transcription Factors*
  • Translocation, Genetic*

Substances

  • 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