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Cancers (Basel). 2019 Nov 11;11(11). pii: E1774. doi: 10.3390/cancers11111774.

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

Author information

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.

Abstract

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.

KEYWORDS:

ARPP-19; MRD; PME-1; SET; WT1; cancer

PMID:
31717978
DOI:
10.3390/cancers11111774
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