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B cell receptor sig...
B cell receptor signaling suppressor SHP-1 is active in CLL lymph node and peripheral blood
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- Bergh, Ann-Charlotte (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- El-Schich, Zahra (författare)
- Department of Biomedical Science, Health and Society, Malmö University, Malmö, Sweden
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- Delfani, Payam (författare)
- Department of Immunotechnology, Lund Institute of Technology, Lund University, Lund, Sweden
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- Ohlsson, Lars (författare)
- Department of Biomedical Science, Health and Society, Malmö University, Malmö, Sweden
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- Rosén, Anders (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Gjörloff Wingren, Anette (författare)
- Department of Biomedical Science, Health and Society, Malmö University, Malmö, Sweden
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Protein tyrosine phosphatase SHP-1 expression and activity is downregulated or lost in several leukemias and lymphomas due to DNA promotor hypermethylation, catalytic site mutation or oxidation, or phosphorylation at inhibitory sites, implying a negative role of SHP-1 in development of leukemias/lymphomas. In chronic lymphocytic leukemia (CLL), B cell receptor (BcR) and microenvironment signal levels are important in the pathogenesis. Considering that SHP-1 is a BcR signaling suppressor, we hypothesized that SHP-1 would be down-regulated and/or inactivated in the proliferative center lymph node (LN) cells. We analyzed PTPN6 (SHP-1) gene expression, SHP-1 protein expression and phosphorylation status in matched CD5+/CD19+ peripheral blood (PB) and LN cells from 6 CLL patients, and in comparison, BcR (anti-IgM) in vitro triggered CLL PB cells from 10 patients. Gene expression of PTPN6 was significantly higher in PB compared to LN CLL cells in 50% of the cases. SHP-1 protein expression level and phosphorylation at SHP-1Y536 and SHP-1S591 were, however, equal in PB and LN samples. SHP-1 phosphorylation at Y536 and S591, in PB CLL cells cultured ex vivo was significantly reduced upon BcR engagement in all patient samples. These results indicate that in vivo BcR signaling in CLL is paralyzed.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- B cell
- chronic lymphocytic leukemia
- SHP-1
- suppressor
- tyrosine phosphorylation
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)