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  • Original Paper
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Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in myeloid leukemia and other malignant cells

Oncogene volume 22, pages 7649–7660 (2003)Cite this article

Abstract

Northern blotting confirmed previous results indicating that the mitogen-activated protein kinase (MAPK) phosphatase Pyst2-L was highly expressed in leukocytes obtained from acute myeloid leukemia (AML) patients. High levels of Pyst2-L mRNA were expressed in bone marrow (BM) and peripheral leukocytes from nine AML and acute lymphoblastic leukemia (ALL) patients. BM from healthy individuals expressed very low levels of Pyst2-L. Whereas high levels of Pyst2-L mRNA and protein were detected in several leukemia cell lines, Pyst2-L mRNA was detected neither in 33/34 samples of normal peripheral blood mononuclear cells (PBMC) nor in leukocyte fractions enriched with CD34+ cells. Certain solid tumor and lymphoblastoid cell lines expressed high levels of Pyst2-L mRNA. In view of the association of Pyst2-L to MAPK signaling cascades, we tested if cell activation, a process involving MAPK signaling, influences Pyst2-L expression. Indeed, activation of T cells and endothelial cells increased Pyst2-L in these cells. Furthermore, TPA, a known MAPK activator, induces the expression of both Pyst2-L mRNA as well as the Pyst2-L protein in leukemia cells. This induction was partially inhibited by PD098059, an Mek1/2-specific inhibitor. Based on the results of this and previous studies, we hypothesize that the high levels of Pyst2-L detected in the active state of AML and ALL diseases and in other types of cancer reflect an altered MAPK signaling pathway in such malignant processes. This alteration may be the result of a failed attempt to counter the constitutive activation of MAPK in transformed cells or alternatively, may represent the activated state of such cells.

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Abbreviations

AML:

acute myeloid leukemia

ML:

myeloid leukemia

ALL:

acute lymphoblastic leukemia

MAPK:

mitogen-activated protein kinase

DUSP:

dual-specificity phosphatases

BM:

bone marrow

PBMC:

peripheral blood mononuclear cells

HUVEC:

human umbilical cord vein endothelial cells

TPA:

12-O-tetradecanoylphorbol-13-acetate

FN:

fibronectin

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Acknowledgements

This study was supported by the Gabrielle Rich Leukemia Research Foundation Lucerne, Switzerland and by the James J Leibman and Rita S Leibman Endowment Fund for Cancer Research. IP Witz is the incumbent of the David Furman Chair in Immunobiology of Cancer.

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Authors and Affiliations

  1. Department of Cell Research and Immunology, George S Wise Faculty of Life Sciences, Tel-Aviv, Israel

    Orlev Levy-Nissenbaum, Orit Sagi-Assif, Dina Kapon, Shay Hantisteanu, Tamar Burg & Isaac P Witz

  2. The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel-Aviv University, Tel-Aviv, Israel

    Orlev Levy-Nissenbaum, Orit Sagi-Assif, Dina Kapon, Shay Hantisteanu, Tamar Burg & Isaac P Witz

  3. Institute of Hematology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Pia Raanani, Abraham Avigdor & Isaac Ben-Bassat

  4. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Pia Raanani, Abraham Avigdor & Isaac Ben-Bassat

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  1. Orlev Levy-Nissenbaum
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Levy-Nissenbaum, O., Sagi-Assif, O., Kapon, D. et al. Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in myeloid leukemia and other malignant cells. Oncogene 22, 7649–7660 (2003). https://doi.org/10.1038/sj.onc.1206971

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