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Updated: Jun 27, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Protein-tyrosine phosphatase activity maintains the viability of hairy cells and modulates their response to
David Allsup1, Robert Harris, Peter Baker
1Department of Haematology, Hull and East Yorkshire Hospitals NHS Trust, Hull, East Yorkshire, England, UK. david.allsup@hey.nhs.uk
Abstract:
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.
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