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Overexpression of Orphan Receptor Tyrosine Kinase Ror1 as a Putative Tumor-Associated Antigen in Iranian Patients with Acute Lymphoblastic LeukemiaShabani M.a · Asgarian Omran H.a · Jeddi-Tehrani M.b, g · Vossough P.d · Faranoush M.d · Sharifian R.A.e · Toughe G.R.e · Kordmahin M.e · Khoshnoodi J.a · Roohi A.a · Tavoosi N.c · Mellstedt H.g · Rabbani H.c, g · Shokri F.a, b, f
aDepartment of Immunology, School of Public Health, Medical Sciences/University of Tehran, bMonoclonal Antibody Research Center and cDepartment of Reproductive Immunology, Reproductive Biotechnology Research Center, Avesina Research Institute, dClinic of Hematology, Ali-Asghar Hospital, Faculty of Medicine, Iran University of Medical Sciences, eClinic of Hematology and Oncology, Vali-Asr Hospital, Faculty of Medicine, Medical Sciences/University of Tehran, fNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran, and gImmune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
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.
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