Reader TTS

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. Access

through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal

Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may

be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support

SIMILAR CONTENT BEING VIEWED BY OTHERS FBXO11 IS A CANDIDATE TUMOR SUPPRESSOR IN THE LEUKEMIC TRANSFORMATION OF MYELODYSPLASTIC SYNDROME Article Open access 06 October 2020 MUSASHI 2

INFLUENCES CHRONIC LYMPHOCYTIC LEUKEMIA CELL SURVIVAL AND GROWTH MAKING IT A POTENTIAL THERAPEUTIC TARGET Article Open access 27 January 2021 PROTEIN ARGININE METHYLTRANSFERASE 2 CONTROLS

INFLAMMATORY SIGNALING IN ACUTE MYELOID LEUKEMIA Article Open access 20 June 2024 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 REFERENCES * Adams PD and Parker PJ . (1991). _FEBS Lett._, 290, 77–82. * Andersen JN, Elson A, Lammers R, Romer J, Clausen

JT, Moller KB and Moller NP . (2001). _Biochem. J._, 354, 581–590. * Babcock GJ, Hochberg D and Thorley-Lawson AD . (2000). _Immunity_, 13, 497–506. * Ballif BA and Blenis J . (2001). _Cell

Growth Differ._, 12, 397–408. * Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E and Larizza L . (2000). _Hum. Mol. Genet._, 9, 2297–2304. * Berndt N . (1999). _Front.

Biosci._, 4, D22–D42. * Biethahn S, Alves F, Wilde S, Hiddemann W and Spiekermann K . (1999). _Exp. Hematol._, 27, 885–894. * Chorvath B, Duraj J and Stockbauer P . (1983). _Neoplasma_, 30,

273–280. * Chu Y, Solski PA, Khosravi-Far R, Der CJ and Kelly K . (1996). _J. Biol. Chem._, 271, 6497–6501. * Dahia PL . (2000). _Endocr. Relat. Cancer_, 7, 115–129. * Dickinson RJ, Williams

DJ, Slack DN, Williamson J, Seternes OM and Keyse SM . (2002). _Biochem. J._, 364, 145–155. * Dowd S, Sneddon AA and Keyse SM . (1998). _J. Cell Sci._, 111, 3389–3399. * Dudley DT, Pang L,

Decker SJ, Bridges AJ and Saltiel AR . (1995). _Proc. Natl. Acad. Sci. USA_, 92, 7686–7689. * Eckstein JW . (2000). _Invest. New Drugs_, 18, 149–156. * Eshel R, Besser M, Zanin A, Sagi-Assif

O and Witz IP . (2001). _Cell Immunol._, 213, 141–148. * Eshel R, Zanin A, Sagi-Assif O, Meshel T, Smorodinsky NI, Dwir O, Alon R, Brakenhoff R, van Dongen G and Witz IP . (2000). _J. Biol.

Chem._, 275, 12833–12840. * Frearson JA and Alexander DR . (1996). _Immunol. Today_, 17, 385–391. * Galaktionov K, Lee AK, Eckstein J, Draetta G, Meckler J, Loda M and Beach D . (1995).

_Science_, 269, 1575–1577. * Geller RB and Bray RA . (1997). _Leukemia Res._, 21, 387–389. * Gopalakrishna R, Gundimeda U, Fontana JA and Clarke R . (1999). _Cancer Lett._, 136, 143–151. *

Groom LA, Sneddon AA, Alessi DR, Dowd S and Keyse SM . (1996). _EMBO J._, 15, 3621–3632. * Hantisteanu S, Levy-Nissenbaum O, Sagi-Assif O, Raanani P, Avigdor A, Ben-Bassat I and Witz I .

(2002). _Proceedings of the Second International Conference on Tumor Microenvironment: Progression, Therapy and Prevention. Baden, Austria_, Manduzzi Editore. Witz IP (ed). S.p.A., Bologna,

Italy, 95–100. Google Scholar  * Hass R, Bartels H, Topley N, Hadam M, Kohler L, Goppelt-Strube M and Resch K . (1989). _Eur. J. Cell Biol._, 48, 282–293. * He H, Wang X, Gorospe M, Holbrook

NJ and Trush MA . (1999). _Cell Growth Differ._, 10, 307–315. * Hernandez S, Hernandez L, Bea S, Cazorla M, Fernandez PL, Nadal A, Muntane J, Mallofre C, Montserrat E, Cardesa A and Campo E

. (1998). _Cancer Res._, 58, 1762–1767. * Horn S, Meyer J, Heukeshoven J, Fehse B, Schulze C, Li S, Frey J, Poll S, Stocking C and Jucker M . (2001). _Leukemia_, 15, 112–120. * Hwang PH, Yi

HK, Kim DS, Nam SY, Kim JS and Lee DY . (2001). _Cancer Lett._, 172, 83–91. * Jaffe EA, Nachman RL, Becker CG and Minick CR . (1973). _J. Clin. Invest._, 52, 2745–2756. * Johnson TR, Biggs

JR, Winbourn SE and Kraft AS . (2000). _J. Biol. Chem._, 275, 31755–31762. * Keyse SM and Ginsburg M . (1993). _Trends Biochem. Sci._, 18, 377–378. * Klint P, Kanda S, Kloog Y and

Claesson-Welsh L . (1999). _Oncogene_, 18, 3354–3364. * Koeffler HP, Bar-Eli M and Territo MC . (1981). _Cancer Res._, 41, 919–926. * Lee Jr JT and McCubrey JA . (2002). _Leukemia_, 16,

486–507. * Levy-Nissenbaum O, Sagi-Assif O, Hantisteanu S, Raanani P, Avigdor A, Ben-Bassat I and Witz I . (2002). _Proceedings of the Second International Conference on Tumor

Microenvironment: Progression, Therapy and Prevention. Baden, Austria_. Manduzzi Editore. Witz IP (ed). S.p.A., Bologna, Italy, pp. 11–17. Google Scholar  * Levy-Nissenbaum O, Sagi-Assif O,

Raanani P, Avigdor A, Ben-Bassat I and Witz I . (2003a). _Methods Enzymol._ (in press). * Levy-Nissenbaum O, Sagi-Assif O, Raanani P, Avigdor A, Ben-Bassat I and Witz I . (2003b). _Cancer

Lett._ (in press). * Levy-Nissenbaum O, Sagi-Assif O and Witz I . (2003c). _Genes, Chromosomes and Cancer_. (submitted for publication). * Marshall CJ . (1994a). _Curr. Opin. Genet. Dev._,

4, 82–89. * Marshall CJ . (1994b). _Nature_, 367, 686. * Mercurius KO and Morla AO . (2001). _BMC Cell. Biol._, 2, 18. * Molla A and Block MR . (2000). _Cell Growth Differ._, 11, 83–90. *

Moore S, McDiarmid LA and Hughes TP . (2000). _Leukemia Lymphoma_, 38, 211–220. * Muda M, Boschert U, Smith A, Antonsson B, Gillieron C, Chabert C, Camps M, Martinou I, Ashworth A and

Arkinstall S . (1997). _J. Biol. Chem._, 272, 5141–5151. * Nilsson I and Hoffmann I . (2000). _Prog. Cell. Cycle Res._, 4, 107–114. * Ofek P, Ben-Meir D, Kariv-Inbal Z, Oren M and Lavi S .

(2003). _J. Biol. Chem._, 278 (16), 14299–14305. * Parsons R . (1998). _Curr. Opin. Oncol._, 10, 88–91. * Pestell KE, Ducruet AP, Wipf P and Lazo JS . (2000). _Oncogene_, 19, 6607–6612. *

Poetsch M, Dittberner T and Woenckhaus C . (2001). _Cancer Genet. Cytogenet._, 125, 21–26. * Rivedal E and Opsahl H . (2001). _Carcinogenesis_, 22, 1543–1550. * Romagnani S . (1995). _J.

Clin. Immunol._, 15, 121–129. * Sambrook J, Fritsch E and Maniatis T . (1989). _Molecular cloning_. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, New York. Google Scholar  * Sano

K, Hayakawa A, Piao JH, Kosaka Y and Nakamura H . (2000). _Blood_, 95, 1066–1068. * Saxena M and Mustelin T . (2000). _Semin. Immunol._, 12, 387–396. * Sebolt-Leopold JS . (2000).

_Oncogene_, 19, 6594–6599. * Seger R and Krebs EG . (1995). _FASEB J._, 9, 726–735. * Shi G, Weh HJ, Martensen S, Seeger D and Hossfeld DK . (1996). _Cytogenet. Cell Genet._, 74, 295–299. *

Shin DY, Ishibashi T, Choi TS, Chung E, Chung IY, Aaronson SA and Bottaro DP . (1997). _Oncogene_, 14, 2633–2639. * Steinitz M, Klein G, Koskimies S and Makel O . (1977). _Nature_, 269,

420–422. * Tanuma N, Nakamura K, Shima H and Kikuchi K . (2000). _J. Biol. Chem._, 275, 28216–28221. * Theodosiou A and Ashworth A . (2002). _Genome Biol._, 3 (Reviews3009), 350–351. *

Wagers AJ, Waters CM, Stoolman LM and Kansas GS . (1998). _J. Exp. Med._, 188, 2225–2231. * Weinstein R, Riordan MA, Wenc K, Kreczko S, Zhou M and Dainiak N . (1989). _Blood_, 73, 111–116. *

Wilkinson MG and Millar JB . (2000). _FASEB J._, 14, 2147–2157. * Wu W, Fan YH, Kemp BL, Walsh G and Mao L . (1998). _Cancer Res._, 58, 4082–4085. * Yamamoto M, Suzuki Y, Kihira H, Miwa H,

Kita K, Nagao M, Tamura S, Shiku H and Nishikawa M . (1999). _Leukemia_, 13, 595–600. Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * 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 * Institute of Hematology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel Pia

Raanani, Abraham Avigdor & Isaac Ben-Bassat * Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Pia Raanani, Abraham Avigdor & Isaac Ben-Bassat Authors * Orlev

Levy-Nissenbaum View author publications You can also search for this author inPubMed Google Scholar * Orit Sagi-Assif View author publications You can also search for this author inPubMed 

Google Scholar * Dina Kapon View author publications You can also search for this author inPubMed Google Scholar * Shay Hantisteanu View author publications You can also search for this

author inPubMed Google Scholar * Tamar Burg View author publications You can also search for this author inPubMed Google Scholar * Pia Raanani View author publications You can also search

for this author inPubMed Google Scholar * Abraham Avigdor View author publications You can also search for this author inPubMed Google Scholar * Isaac Ben-Bassat View author publications You

can also search for this author inPubMed Google Scholar * Isaac P Witz View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR

Correspondence to Isaac P Witz. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download

citation * Received: 26 February 2003 * Revised: 02 July 2003 * Accepted: 10 July 2003 * Published: 23 October 2003 * Issue Date: 23 October 2003 * DOI:

https://doi.org/10.1038/sj.onc.1206971 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Pyst2 * leukemia * dual-specificity phosphatases * DNA

microarray * cell activation * differentiation