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Article

Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia

1
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
2
Institute of Biomedicine, University of Turku, 20520 Turku, Finland
3
Turku Doctoral Programme of Molecular Medicine, 20520 Turku, Finland
4
Department of Biostatistics, University of Turku, 20520 Turku, Finland
5
Department of Hematology, Turku University Hospital (TYKS), 20521 Turku, Finland
6
Central Laboratory, Turku University Hospital (TYKS), 20521 Turku, Finland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1774; https://doi.org/10.3390/cancers11111774
Received: 22 October 2019 / Revised: 5 November 2019 / Accepted: 6 November 2019 / Published: 11 November 2019
(This article belongs to the Special Issue Acute Myeloid Leukemia)
Disease relapse from standard chemotherapy in acute myeloid leukemia (AML) is poorly understood. The importance of protein phosphatase 2A (PP2A) as an AML tumor suppressor is emerging. Therefore, here, we examined the potential role of endogenous PP2A inhibitor proteins as biomarkers predicting AML relapse in a standard patient population by using three independent patient materials: cohort1 (n = 80), cohort2 (n = 48) and The Cancer Genome Atlas Acute Myeloid Leukemia (TCGA LAML) dataset (n = 160). Out of the examined PP2A inhibitors (CIP2A, SET, PME1, ARPP19 and TIPRL), expression of ARPP19 mRNA was found to be independent of the current AML risk classification. Functionally, ARPP19 promoted AML cell viability and expression of oncoproteins MYC, CDK1, and CIP2A. Clinically, ARPP19 mRNA expression was significantly lower at diagnosis (p = 0.035) in patients whose disease did not relapse after standard chemotherapy. ARPP19 was an independent predictor for relapse both in univariable (p = 0.007) and in multivariable analyses (p = 0.0001) and gave additive information to EVI1 expression and risk group status (additive effect, p = 0.005). Low ARPP19 expression was also associated with better patient outcome in the TCGA LAML cohort (p = 0.019). In addition, in matched patient samples from diagnosis, remission and relapse phases, ARPP19 expression was associated with disease activity (p = 0.034), indicating its potential usefulness as a minimal residual disease (MRD) marker. Together, these data demonstrate the oncogenic function of ARPP19 in AML and its risk group independent role in predicting AML patient relapse tendency. View Full-Text
Keywords: cancer; ARPP-19; PME-1; SET; WT1; MRD cancer; ARPP-19; PME-1; SET; WT1; MRD
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MDPI and ACS Style

Mäkelä, E.; Löyttyniemi, E.; Salmenniemi, U.; Kauko, O.; Varila, T.; Kairisto, V.; Itälä-Remes, M.; Westermarck, J. Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia. Cancers 2019, 11, 1774. https://doi.org/10.3390/cancers11111774

AMA Style

Mäkelä E, Löyttyniemi E, Salmenniemi U, Kauko O, Varila T, Kairisto V, Itälä-Remes M, Westermarck J. Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia. Cancers. 2019; 11(11):1774. https://doi.org/10.3390/cancers11111774

Chicago/Turabian Style

Mäkelä, Eleonora, Eliisa Löyttyniemi, Urpu Salmenniemi, Otto Kauko, Taru Varila, Veli Kairisto, Maija Itälä-Remes, and Jukka Westermarck. 2019. "Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia" Cancers 11, no. 11: 1774. https://doi.org/10.3390/cancers11111774

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