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Phosphatase PRL2 promotes AML1-ETO-induced acute myeloid leukemia

Leukemia volume 31, pages 1453–1457 (2017)Cite this article

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Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy with poor prognosis.1 Core-binding factor AML is cytogenetically defined by the presence of t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), commonly abbreviated as t(8;21) and inv(16), respectively.2, 3 In both subtypes, the cytogenetic rearrangements disrupt genes that encode subunits of core-binding factor, a transcription factor that functions as an essential regulator of normal hematopoiesis.2, 3 The t(8;21) translocation, which generates the AML1-ETO fusion gene, is one of the most common chromosomal abnormalities detected in AML.4 The AML1-ETO fusion transcription factor is present in ~4–12% of adult and 12–30% of pediatric AML patients.4 AML1-ETO+ AML remains a significant clinical problem, with 30% of patients relapsing and long‐term survival rates ranging between 30 and 60%, indicating the need for improved therapeutic approaches.2, 3, 4

The phosphatase of regenerating liver (PRL) family of phosphatases, consisting of PRL1, PRL2 and PRL3, represents an intriguing group of proteins being validated as biomarkers and therapeutic targets in human cancer.5 Notably, recent findings indicate that PRLs may have important roles in the pathogenesis of hematological malignancies.6 Both PRL2 and PRL3 are highly expressed in some hematological malignancies, including AML, CML, multiple myeloma and acute lymphoblastic leukemia (ALL).6 High PRL3 mRNA expression is associated with FLT3-ITD mutations and poor prognosis in AML patients with normal karyotype.7 We have identified PRL2 to be important for the proliferation and self-renewal of hematopoietic stem cells through the regulation of KIT signaling.8 Recently, we found that PRL2 mediates NOTCH and KIT signals in early T-cell progenitors and that PRL2 is essential for oncogenic NOTCH1-induced T-cell leukemia in vivo.9, 10 An improved understanding of how PRLs function and how they are regulated may establish PRLs as novel therapeutic targets in AML.

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Acknowledgements

This work was supported, in part, by National Institutes of Health Grant CA69202 (to ZYZ), Department of Defense Grant W81XWH-13-1-0187 (to YL), a St Baldrick’s Foundation Scholar Award (to YL), an Elsa Pardee Foundation New Investigator Award (to YL), an Alex’s Lemonade Stand Foundation Grant (to YL), a Children’s Leukemia Research Association Grant (to YL), a Leukemia Research Foundation grant (to YL) and American Cancer Society Institutional Research Grants (to YL and MK). This work was supported by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108. We also thank Marilyn Wales and John Spence for helping the preparation of the manuscript.

Author contributions

MK, SC, YB, ZYZ and YL: designed the research. MK, SC, YB, CY, RG, XJS, CM, TAT and ZHY: performed the research; MK and YL: analyzed the data and performed the statistical analysis. HSB, MCY, RK and JCM: provided reagents to the study. ZYZ and YL: wrote the manuscript. All authors read, commented on and approved the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    M Kobayashi, R Gao, C Mu, T A Twiggs, M C Yoder, R Kapur & Y Liu

  2. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    S Chen & Y Liu

  3. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA

    Y Bai, Z-H Yu & Z-Y Zhang

  4. Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    C Yao

  5. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    X-J Sun

  6. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    H S Boswell

  7. Cancer and Blood Disease Institute, Cincinnati Children's Hospital Research Center, Cincinnati, OH, USA

    J C Mulloy

Authors
  1. M Kobayashi
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  14. Z-Y Zhang
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  15. Y Liu
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Corresponding authors

Correspondence to Z-Y Zhang or Y Liu.

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Kobayashi, M., Chen, S., Bai, Y. et al. Phosphatase PRL2 promotes AML1-ETO-induced acute myeloid leukemia. Leukemia 31, 1453–1457 (2017). https://doi.org/10.1038/leu.2017.67

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