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Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy
- Source :
- International Journal of Cancer. 123:1190-1195
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Gene profiling studies of patients with chronic lymphocytic leukemia (CLL) has revealed increased expression of Ror1, a cell surface receptor tyrosine kinase. The aim of present study was to analyze gene and protein expression of Ror1 in CLL cells and normal blood leukocytes. Gene expression analysis reverse transcriptionpolymerase chain reaction of ROR1 revealed that all patients with CLL (n 5 100) spontaneously expressed ROR1 mRNA whereas enriched blood B and T cells as well as granulocytes from healthy donors (n 5 10) were negative. A strong nonphysiological activation signal (PMA/ionomycin) was required to induce expression in vitro in normal lymphocytes. Major genomic aberrations (mutations or truncation) of ROR1 were not observed. Protein expression was analyzed by Western blot using a panel of polyclonal anti-Ror antibodies as well as flow cytometry. Blood lymphocytes from 18/18 CLL patients, but none of the 10 healthy donors, expressed surface Ror1. The majority of CLL cells exhibited Ror1 surface expression (71% mean; range 36–92%) with a mean fluorescence intensity (MFI) of 20 (range 10–45). The corresponding MFI of CD19 on CLL cells was 26 (range 9–48). There was no difference in the Ror1 protein expression comparing IgVH mutated and unmutated cases as well as progressive and nonprogressive CLL patients. Two different variants of the Ror1 protein, 105 and 130 kDa, were identified. The Ror1 protein expression in patients with CLL but not in normal leukocytes merits further studies of its role in the pathobiology of CLL, which may provide a basis for development of Ror1 directed targeted therapy. ' 2008 Wiley-Liss, Inc.
- Subjects :
- Cancer Research
T-Lymphocytes
Chronic lymphocytic leukemia
Blotting, Western
Receptor Tyrosine Kinase-like Orphan Receptors
Gene Expression Regulation, Enzymologic
Receptor tyrosine kinase
CD19
BCL9
Cell surface receptor
hemic and lymphatic diseases
medicine
Humans
RNA, Messenger
In Situ Hybridization, Fluorescence
B-Lymphocytes
biology
Reverse Transcriptase Polymerase Chain Reaction
Cirmtuzumab
Receptor Protein-Tyrosine Kinases
Flow Cytometry
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
Gene Expression Regulation, Neoplastic
Oncology
ROR1
Leukocytes, Mononuclear
biology.protein
Cancer research
Tyrosine kinase
Granulocytes
Subjects
Details
- ISSN :
- 10970215 and 00207136
- Volume :
- 123
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi.dedup.....3959f1caff95316db28219a3ed098cb0