title: The receptor tyrosine kinase p185HER2 is expressed on a subset of B-lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia.
abstract: The class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B-lymphoblastic leukemias.
authors.affiliation: Second Department of Internal Medicine, University of Tübingen, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bühring
authors.forename: I
authors.initials: I
authors.lastname: Sures
authors.forename: B
authors.initials: B
authors.lastname: Jallal
authors.forename: F U
authors.initials: FU
authors.lastname: Weiss
authors.forename: F W
authors.initials: FW
authors.lastname: Busch
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.forename: H D
authors.initials: HD
authors.lastname: Waller
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D016175:B-Lymphocyte Subsets / Q000201:enzymology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001752:Blast Crisis; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D019000:Phosphotyrosine; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D014443:Tyrosine