Overexpression of Orphan Receptor Tyrosine Kinase <i>Ror1</i> as a Putative Tumor-Associated Antigen in Iranian Patients with Acute Lymphoblastic Leukemia

Abstract

Receptor tyrosine kinases (RTKs) are a group of enzymes involved in a variety of physiological and pathological processes. The human Ror1 is a member of the RTK family with unknown ligand and biological function. Overexpression of Ror1 has recently been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to explore the expression profile of Ror1 in acute lymphoblastic leukemia (ALL) cells. Therefore, leukemic cells were isolated from the bone marrow and/or peripheral blood (PB) of 57 ALL patients. Immunophenotyping was performed by flow cytometry and mRNA expression was detected by RT-PCR. Overexpression of Ror1 mRNA was detected in 23 of 57 (40%) ALL patients. A similar expression pattern was observed in ALL cell lines, with 4 of 12 (33%) being positive. Stimulation of normal PB mononuclear cells with pokeweed mitogen and phorbol myristate acetate induced substantially higher Ror1 mRNA expression compared to unstimulated cultured cells. There has been neither a significant association between Ror1 expression and the immunophenotypic profile of the leukemic cells, nor with other clinical or hematological features of the patients. In conclusion, our findings propose Ror1 as a new tumor-associated antigen and a potential tool for targeted immunotherapy and monitoring of minimal residual disease in ALL.

ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo

“…Restricted expression of receptor tyrosine kinase ROR1 in several B-cell malignancies, including MCL, chronic lymphocytic leukemia, and subsets of pediatric acute lymphoblastic leukemia, has been reported [5,6,[10][11][12]. Consistent with this, JeKo, Mino ( Fig.…”

MYBPC1 Computational Phosphoprotein Network Construction and Analysis between Frontal Cortex of HIV encephalitis (HIVE) and HIVE-Control Patients

“…ROR1 was identified by molecular function of receptor, tyrosine protein kinase receptor, kinase, protein kinase, and protein kinase receptor, and by biological process of protein metabolism and modification, protein modification, protein phosphorylation, signal transduction, cell surface receptor-mediated signal transduction and receptor protein tyrosine kinase signaling pathway (DAVID database). ROR1's relational study also could be presented in these articles (Baskar et al 2008;Daneshmanesh et al 2008;Fukuda et al 2008;Shabani et al 2007Shabani et al , 2008. CREB5's molecular function consisted of transcription factor and nucleic acid binding, and it was involved in biological process of nucleoside, nucleotide and nucleic acid metabolism, mRNA transcription, mRNA transcription regulation, signal transduction, and intracellular signaling cascade (DAVID database).…”

Production and Characterization of a Peptide-based Monoclonal Antibody Against CD44 Variant 6

“…The eluted antibodies were dialyzed against PBS at pH 7.5, and reactivity of the purified antibodies was determined by ELISA, as described previously. (18,19) The isotypes of the antibodies were determined by ELISA using anti mouse isotype antibodies (Sigma-Aldrich) as reported previously. (20) Analysis of antibody titers by ELISA Peptide-specific antibodies in the mouse sera and in hybridoma culture supernatants were determined by indirect ELISA.…”

“…Total RNA was extracted from cell lines according to guanidinium thiocyanate-phenol-chloroform extraction method (18) using RNA-Bee reagent (Tel-Test, Friendswood, TX) according to the manufacturer's instructions. The extracted RNA was treated with deoxyribonuclease (DNAase I, Sigma-Aldrich) to eliminate any potential DNA contamination.…”