Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia
Abstract
:1. Background
2. Materials and Methods
2.1. Patient Cohorts
2.2. Statistical Analysis
2.3. RNA Isolation and cDNA Synthesis
2.4. Quantitative Real-Time PCR (RQ-PCR)
2.5. Cell Culture
2.6. Antibodies
2.7. Western Blot Assay
2.8. siRNAs, shRNAs and Cell Viability Assay
3. Results
3.1. PP2A Inhibitor Protein mRNA Expression in AML Patient Cohort
3.2. ARPP19 Expression Promotes AML Cell Survival
3.3. ARPP19 Promotes Expression of Oncogenic Drivers MYC, CDK1 and CIP2A in AML Cells
3.4. Low ARPP19 mRNA Expression is an Independent Predictive Relapse Marker
3.5. Uni- and Multivariable Analyses
3.6. Survival Analysis Based on PP2A Inhibitor Protein mRNA Expression in AML Patients
3.7. ARPP19 Expression Correlates with AML Disease Activity after Remission
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AML | acute myeloid leukemia |
ARPP19 | cAMP-regulated phosphoprotein 19 |
HSCT | hematopoietic stem cell transplantation |
PAIP | PP2A inhibitor protein |
PP2A | protein phosphatase 2A |
RQ-PCR | real-time quantitative PCR |
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Parameter | Time to Relapse | ||
---|---|---|---|
Hazard Ratio | 95% CI | p | |
Riskgroup | 0.017 | ||
EVI1 | 1.26 | 1.11 to 1.44 | 0.0005 |
SET | 2.36 | 1.06 to 5.25 | 0.035 |
ARPP19 | 2.87 | 1.33 to 6.22 | 0.007 |
Parameter | Time to Relapse | Overall Survival | ||
---|---|---|---|---|
Hazard Ratio | p | Hazard Ratio | p | |
Diagnosis age | 1.07 | 0.023 | 1.07 | 0.0004 |
NPM1 mutation | 0.03 | 0.048 | 0.21 | 0.017 |
EVI1 | 1.41 | 0.0005 | 1.14 | 0.026 |
SET | 0.12 | 0.010 | ||
ARPP19 | 58.77 | 0.0001 | 2.05 | 0.046 |
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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
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 StyleMäkelä, 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
APA StyleMäkelä, E., Löyttyniemi, E., Salmenniemi, U., Kauko, O., Varila, T., Kairisto, V., Itälä-Remes, M., & Westermarck, J. (2019). Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia. Cancers, 11(11), 1774. https://doi.org/10.3390/cancers11111774