Specific Monoclonal Antibody Against Bcr/Abl Out-of-Frame Alternative Proteins as Diagnostic Tool in Chronic Myelogenous Leukemia Patients

Claudia Casnici, Katia Crotta, Gisella Volpe, Cristina Panuzzo, Donatella Lattuada, Giulia Mesiano, Giuseppe Saglio, Ornella Marelli

Research output: Contribution to journalArticle

Abstract

More recently, alternative splicing of specific genes are investigated for their therapeutic potential. In particular, we reported the existence of BCR-ABL alternative splicing isoforms, in about 80% of Philadelphia-positive patients, which lead to the expression of aberrant proteins. These fusion proteins are characterized by an orphan initial and correct Bcr portion attached to a 112 amino acid sequence, arising from the impairment in the reading frame (reading of ABL exon 4 and 5). We demonstrated that these Abl-out-of-frame (OOF) isoforms could have an immunological role with therapeutic implications. The aim of this study was to characterize a new monoclonal antibody (MAb) specific for Abl-OOF protein portion, for diagnostic use, to detect this biomarker in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients and to generate novel approaches in the immunotherapy. 5F11G11 MAb recognizes the OOF protein portion of the native full-length Bcr/Abl-OOF protein expressed in cells transiently transfected, as demonstrated by immunoprecipitation and immunofluorescence. In addition, we demonstrate the MAb's ability to recognize the alternative hybrid Bcr/Abl fusion protein expressed in leukemic cells from CML patients, to support the possible use of 5F11G11 MAb as a diagnostic tool to select patients with Philadelphia chromosome-positive CML that could be eligible for an immunotherapeutic approach with this new antigen.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalMonoclonal Antibodies in Immunodiagnosis and Immunotherapy
Volume36
Issue number4
DOIs
Publication statusPublished - Aug 1 2017

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Keywords

  • BCR/ABL transcripts
  • Chronicmyelogenous leukemia
  • Monoclonal antibody
  • Tumor-associated antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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