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T-cell-receptor-activity shaped miR-omes of T-PLL
clinical survival score that predicts T-PLL patients’ out- comes, based on expression levels of miR-200a-3p, miR- 223-3p, and miR-424-5p.
Clinical management of T-PLL remains challenging and current studies mainly focus on the development of target- ed treatments directed against anti-apoptotic factors like BLC247 or sustained prosurvival signaling mediated via JAK/STAT pathways.48,49 Our study suggests that develop- ing a miR-directed targeting strategy could allow tackling a combination of those pathways and might therefore be a promising approach to successfully eradicate T-PLL cells. However, these concepts have to be tested in subsequent preclincal studies. Furthermore, the presented miROS-T- PLL survival score might help in better discriminating rather indolent versus aggressive T-PLL disease phases at the time of diagnosis.
Contributions
TB, AS, and MH developed the concept of the research; TB, PM, MF, MH and JA acquired the data; TB, MG, LW and MO performed the formal analysis; MG and LW acquired and ana- lyzed the data; TB, LW and AS prepared the original draft and wrote the manuscript; SH and MH wrote, reviewed and edited the mansucript; AS, SH, MH and MHa supervised the work; TB and MO did the project administration. All authors reviewed and approved the final version of the manuscript.
Funding
This research was funded by the DFG Research Unit FOR1961 (Control-T; HE3553/4-2), the Köln Fortune program, and the Fritz Thyssen Foundation (10.15.2.034MN). This work was also funded by the EU Transcan-2 consortium ‘ERANET-PLL’ and by the ERAPerMed consortium ‘JAKSTAT-TARGET’. A.S. was sup- ported by a scholarship of the German José Carreras Leukemia Foundation (DJCLS 03F/2016). We gratefully acknowledge patients with their families for their invaluable contributions.
Disclosures
No conflicts of interest to disclose.
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