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Elevated PTPN2 expression is associated with inferior molecular response in de-novo chronic myeloid leukaemia patients

Leukemia volume 28, pages 702–705 (2014)Cite this article

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Chronic myeloid leukaemia (CML) is characterised by the t(9;22)(q34;q11) translocation, resulting in the Bcr-Abl oncoprotein which can be targeted by tyrosine kinase inhibitors (TKIs). However, the clinical response to TKIs between patients is highly variable. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is a member of the protein tyrosine phosphatase family. PTPN2 gene expression is associated with ‘stemness’ across the haematopoietic stem cell, embryonic stem cell and neural stem cell subpopulations.1 PTPN2 has also been shown to regulate the functions of Bcr-Abl and c-Abl,2 as well as the phosphorylation status of STAT13 and STAT5.4 Previous studies have demonstrated that reduced PTPN2 expression is associated with resistance to imatinib, but sensitivity to interferon-alpha in a BCR-ABL1+ cell line, KT-1.5 However, no studies have been performed investigating PTPN2 expression in primary CML patient samples. Therefore, we sought to investigate the impact of PTPN2 expression on clinical response in a cohort of de-novo chronic-phase CML (CP-CML) patients.

A total of 93 mRNA samples, prepared from patient mononuclear cells (MNCs) isolated from blood collected at diagnosis (prior to imatinib treatment), were analysed. PTPN2 gene expression was measured using the Affymetrix Human Gene 1.0 ST microarray, as previously described.6 Briefly, analysis of the microarray data included normalisation by Robust multi-array average (RMA) using the aroma.affymetrix package, with custom annotation (Brainarray Entrez Gene 16.0), in the R statistical program (v2.15.1). Event-free survival (EFS) and mutation-free survival (MFS) were calculated by the Kaplan–Meier method using SPSS statistical software (IBM Corporation, Armonk, NY, USA). Molecular responses were calculated by cumulative incidence using a Fine and Gray model implemented in the R package ‘cmprsk’, and by multivariate Cox regression analysis. In the competing risk regression models, an event was defined by achievement of the desired response, while cessation of TKI for any reason (including death) was the competing risk. All further statistical analyses were performed using GraphPad Prism v6.0.

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Acknowledgements

This project is supported by NHMRC project grants. DBW is funded by a PhD scholarship from the Leukaemia Foundation of Australia.

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Authors and Affiliations

  1. Cancer Theme, South Australia Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

    C H Kok, T Leclercq, D B Watkins, V Saunders, J Wang, T P Hughes & D L White

  2. Department of Medicine, Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia

    C H Kok, D B Watkins, J Wang, T P Hughes & D L White

  3. Department of Haematology, SA Pathology, Adelaide, SA, Australia

    T P Hughes

  4. Centre for Cancer Biology, Adelaide, SA, Australia

    T P Hughes & D L White

Authors
  1. C H Kok
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  2. T Leclercq
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  6. T P Hughes
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Correspondence to D L White.

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Kok, C., Leclercq, T., Watkins, D. et al. Elevated PTPN2 expression is associated with inferior molecular response in de-novo chronic myeloid leukaemia patients. Leukemia 28, 702–705 (2014). https://doi.org/10.1038/leu.2013.329

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