Protein-tyrosine phosphatase activity maintains the viability of hairy cells and modulates their response to interferon-alpha.
Hairy-cell leukemia is characterised by a marked sensitivity of the malignant cells to the cytotoxic effects of therapeutically administered interferon-alpha. The aim of this study was to assess the role of protein tyrosine phosphatases in the maintenance of hairy-cell (HC) viability and their sensitivity to interferon-alpha. The selective tyrosine phosphatase inhibitor mpV(pic) killed HCs, but not normal B lymphocytes or chronic lymphotic leukemia (CLL) cells. HCs displayed increased expression of the phosphatases SHP-1 and SHP-2 when compared with normal B lymphocytes. Phosphatase inhibition also enhanced the cytotoxic effect of interferon-alpha against HCs in four of the five cases tested. Therefore, HCs, but not normal B cells or CLL-cells, require tyrosine phosphatase activity for preservation of their viability. In addition, HC sensitivity to interferon is down-regulated by this activity.
Allsup
David
D
Department of Haematology, Hull and East Yorkshire Hospitals NHS Trust, Hull, East Yorkshire, England, UK. david.allsup@hey.nhs.uk
Harris
Robert
R
Baker
Peter
P
Cawley
John
J
D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D016898:Interferon-alpha; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases