Prognostic and Biologic Relevance of Clinically Applicable Long Noncoding RNA Profiling in Older Patients with Cytogenetically Normal Acute Myeloid Leukemia
Autor: | Jessica Kohlschmidt, Dimitrios Papaioannou, Clara D. Bloomfield, Paolo Fadda, Deedra Nicolet, Richard Stone, Andrew J. Carroll, John C. Byrd, Eunice S. Wang, Hatice Gulcin Ozer, Stefano Volinia, Jonathan E. Kolitz, Ramiro Garzon, Krzysztof Mrózek |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Oncology acute myeloid leukemia elderly prognostic relevance cytogenetics Cancer Research medicine.medical_specialty Myeloid acute myeloid leukemia elderly Article cytogenetics NO Transcriptome 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Internal medicine Biomarkers Tumor medicine Humans Neoplasm Metastasis Survival analysis Aged Neoplasm Staging Aged 80 and over business.industry Gene Expression Profiling Middle Aged Prognosis medicine.disease Survival Analysis Long non-coding RNA Gene expression profiling Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cohort Female RNA Long Noncoding DNA microarray business prognostic relevance |
Zdroj: | Molecular Cancer Therapeutics. 18:1451-1459 |
ISSN: | 1538-8514 1535-7163 |
Popis: | We have previously shown that expression levels of 48 long noncoding RNAs (lncRNA) can generate a prognostic lncRNA score that independently associates with outcome of older patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the techniques used to identify and measure prognostic lncRNAs (i.e., RNA sequencing and microarrays) are not tailored for clinical testing. Herein, we report on an assay (based on the nCounter platform) that is designed to produce targeted measurements of prognostic lncRNAs in a clinically applicable manner. We analyzed a new cohort of 76 older patients with CN-AML and found that the nCounter assay yielded reproducible measurements and that the lncRNA score retained its prognostic value; patients with high lncRNA scores had lower complete remission (CR) rates (P = 0.009; 58% vs. 87%), shorter disease-free (P = 0.05; 3-year rates: 0% vs. 21%), overall (OS; P = 0.02, 3-year rates: 10% vs. 29%), and event-free survival (EFS; P = 0.002, 3-year rates: 0% vs. 18%) than patients with low lncRNA scores. In multivariable analyses, the lncRNA score independently associated with CR rates (P = 0.02), OS (P = 0.02), and EFS (P = 0.02). To gain biological insights, we examined our initial cohort of 71 older patients with CN-AML, previously analyzed with RNA sequencing. Genes involved in immune response and B-cell receptor signaling were enriched in patients with high lncRNA scores. We conclude that clinically applicable lncRNA profiling is feasible and potentially useful for risk stratification of older patients with CN-AML. Furthermore, we identify potentially targetable molecular pathways that are active in the high-risk patients with high lncRNA scores. |
Databáze: | OpenAIRE |
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