title: Preclinical model for identification of therapeutic targets for CML offers clues for handling imatinib resistance.
abstract: Success of imatinib in chronic myeloid leukemia (CML) therapy has undoubtedly proved utility of signalling molecules as therapeutic targets. However, development of imatinib resistance and progression to blastic crisis are the current challenges in clinics. To develop therapeutic alternatives for CML, understanding of signalling events downstream of bcr-abl might be helpful. Current CML cell lines do not give comprehensive picture of signalling events involved in pathogenesis of CML. Hence, there is a major unmet need for a better preclinical model for CML. Here, we report on development of RIN9815/bcr-abl, a novel cell line model that mimics signalling events in CML PMNL. Studies on crucial signalling molecules i.e., ras, rac, rhoA and actin in this cell line identified rhoA as the key regulator involved in CML cell function as well as proliferation of both, imatinib sensitive and resistant cells. Hence, RIN9815/bcr-abl could serve as the unique preclinical model in understanding pathogenesis of CML and in drug development.
authors.affiliation: Biochemistry and Cell Biology, Cancer Research Institute, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.
authors.forename: Poonam R
authors.initials: PR
authors.lastname: Molli
authors.affiliation: Biochemistry and Cell Biology, Cancer Research Institute, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.
authors.forename: Madhura B
authors.initials: MB
authors.lastname: Pradhan
authors.affiliation: Animal Sciences, Cancer Research Institute, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.
authors.forename: Arvind D
authors.initials: AD
authors.lastname: Ingle
authors.affiliation: Biochemistry and Cell Biology, Cancer Research Institute, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India. Electronic address: nishigandha.naik@gmail.com.
authors.forename: Nishigandha R
authors.initials: NR
authors.lastname: Naik
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude
chemical_list: D000068877:Imatinib Mesylate
keywords: Actin; Chronic myeloid leukemia (CML); Formyl peptide receptors (FPR); RhoGTPases; Signal transduction