Deletion of ptpn1 induces myeloproliferative neoplasm

Access through your institution Buy or subscribe Deletion of chromosome 20q (del(20q)) is a common chromosomal abnormality associated with myeloid neoplasms including myeloproliferative

neoplasms (MPNs), myelodysplastic syndrome, myelodysplastic syndrome/MPN overlap disorders and acute myeloid leukemia.1, 2 The del(20q) lesion is present in patients with myelofibrosis (MF)

at a high frequency (23%) and is thus considered to be one of the most frequent cytogenetic abnormalities in MF.3 However, the identity of the target tumor suppressor gene(s) within 20q

involved in the pathogenesis of MF and other myeloid neoplasms remains elusive. The _PTPN1_ gene encoding protein tyrosine phosphatase non-receptor type 1 (PTPN1; also known as PTP1B) is

located on human chromosome 20q13.1-q13.2. Both oncogenic and tumor suppressor functions for PTPN1 have been suggested. _PTPN1_ is overexpressed in breast cancer and deletion of Ptpn1

inhibits ErbB2-induced breast tumorigenesis in mice.4 Somatic loss-of-function mutations in _PTPN1_ have been associated with mediastinal B-cell lymphoma and Hodgkin lymphoma.5 Moreover,

ablation of Ptpn1 accelerates B-cell lymphomagenesis and decreases survival in p53-null mice.6 PTPN1 can negatively regulate Janus kinase/signal transducers and activators of transcription

(JAK/STAT) signaling,7 which is frequently found to be activated in MPNs.8 The common occurrence of del(20q) involving the _PTPN1_ locus in MPN and the negative regulatory role of the

corresponding phosphatase in JAK/STAT signaling led us to hypothesize that _PTPN1_ is a potential tumor suppressor gene within 20q involved in MPN. This is a preview of subscription content,

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OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Asimakopoulos FA, White NJ, Nacheva E, Green AR . Molecular analysis of

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al_. MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy. _Elife_ 2013; 2: e00825. Article  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Dr Benjamin

Neel (Laura and Isaac Perlmutter Cancer Center, New York University) for providing the Ptpn1-floxed mouse and Ptpn1 cDNA construct. We also thank Dr Constance Stein (SUNY Upstate Medical

University) for help with fluorescence _in situ_ hybridization analysis. This work was supported by US National Institute of Health (NIH) Grants R21 CA187128 (to GM), R01 HL095685 (to GM),

R01 HL082983 (to JPM), U54 RR019391 (to JPM) and R01 CA113972 (to JPM) and by a grant from the Leukemia and Lymphoma Society TRP 624-13 (to JPM). GM is a Scholar of the Leukemia and Lymphoma

Society. AUTHOR CONTRIBUTIONS FJ performed research, analyzed data and wrote the manuscript; BP, TK, HM and BP collected and analyzed data; YY analyzed data; REH conducted histopathologic

analysis and revised the manuscript; KKB provided study material; JPM provided clinical specimens, analyzed data and revised the manuscript; GM designed the research, analyzed data and wrote

the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA F Jobe, Y Yang & G Mohi * Department of

Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA B Patel, T Kuzmanovic, H Makishima, B Przychodzen & J P Maciejewski *

Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA R E Hutchison * Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania,

Philadelphia, PA, USA K K Bence Authors * F Jobe View author publications You can also search for this author inPubMed Google Scholar * B Patel View author publications You can also search

for this author inPubMed Google Scholar * T Kuzmanovic View author publications You can also search for this author inPubMed Google Scholar * H Makishima View author publications You can

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can also search for this author inPubMed Google Scholar * R E Hutchison View author publications You can also search for this author inPubMed Google Scholar * K K Bence View author

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author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to G Mohi. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no

conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies this paper on the Leukemia website SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION (PDF 2355 KB) RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Jobe, F., Patel, B., Kuzmanovic, T. _et al._ Deletion of Ptpn1 induces myeloproliferative neoplasm. _Leukemia_

31, 1229–1234 (2017). https://doi.org/10.1038/leu.2017.31 Download citation * Published: 23 January 2017 * Issue Date: May 2017 * DOI: https://doi.org/10.1038/leu.2017.31 SHARE THIS ARTICLE

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