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Deletion of Ptpn1 induces myeloproliferative neoplasm

Leukemia volume 31, pages 1229–1234 (2017)Cite this article

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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.

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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.

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Authors and Affiliations

  1. Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA

    F Jobe, Y Yang & G Mohi

  2. 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

  3. Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA

    R E Hutchison

  4. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

    K K Bence

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  1. F Jobe
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  2. B Patel
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  10. G Mohi
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Correspondence to G Mohi.

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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

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