title: Bcr-Abl dependent post-transcriptional activation of NME2 expression is a specific and common feature of chronic myeloid leukemia.
abstract: We have previously identified NME2 (Nm23-H2) as a tumor antigen in a patient with chronic myeloid leukemia (CML). Here we investigated the association between NME2 and Bcr-Abl. NME2 protein was highly overexpressed in the cytoplasm of peripheral blood mononuclear cells from 29/30 patients with CML at diagnosis and 10/10 patients resistant to imatinib. Protein was overexpressed in the absence of increased levels of mRNA and was limited to Bcr-Abl + populations, being absent from Bcr-Abl - patient cells, normal donors and 14/15 acute myeloid leukemia (AML) samples. Furthermore, the Bcr-Abl dependent overexpression of NME2 protein was reversed specifically by tyrosine kinase inhibitor (TKI) treatment of Ba/F3 expressing wild-type and TKI-sensitive, but not TKI-resistant, mutants of Bcr-Abl. The post-transcriptional up-regulation of the tumor antigen NME2 is therefore a common and specific property of CML closely associated with Bcr-Abl activity.
authors.affiliation: Division of Hematology, Internal Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tschiedel
authors.forename: Enrica
authors.initials: E
authors.lastname: Bach
authors.forename: Annette
authors.initials: A
authors.lastname: Jilo
authors.forename: Song-Yau
authors.initials: SY
authors.lastname: Wang
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Haifa-Kathrin
authors.initials: HK
authors.lastname: Al-Ali
authors.forename: Vladan
authors.initials: V
authors.lastname: Vucinic
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Michael
authors.initials: M
authors.lastname: Cross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D001549:Benzamides; D003593:Cytoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000096:biosynthesis*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional
chemical_list: D000951:Antigens, Neoplasm; D001549:Benzamides; D054778:NM23 Nucleoside Diphosphate Kinases; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C517940:NME2 protein, human