Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/85855
Title: | Azacitidine-induced reconstitution of the bone marrow T cell repertoire is associated with superior survival in AML patients |
Author(s): | Grimm, Juliane Simnica, Donjete Jäkel, Nadja Paschold, Lisa Willscher, Edith Schulze, Susann Dierks, Christine Al-Ali, Haifa Kathrin Binder, Mascha |
Issue Date: | 2022 |
Type: | Article |
Language: | English |
Abstract: | Hypomethylating agents (HMA) like azacitidine are licensed for the treatment of acute myeloid leukemia (AML) patients ineligible for allogeneic hematopoietic stem cell transplantation. Biomarker-driven identification of HMA-responsive patients may facilitate the choice of treatment, especially in the challenging subgroup above 60 years of age. Since HMA possesses immunomodulatory functions that constitute part of their anti-tumor effect, we set out to analyze the bone marrow (BM) immune environment by next-generation sequencing of T cell receptor beta (TRB) repertoires in 51 AML patients treated within the RAS-AZIC trial. Patients with elevated pretreatment T cell diversity (11 out of 41 patients) and those with a boost of TRB richness on day 15 after azacitidine treatment (12 out of 46 patients) had longer event-free and overall survival. Both pretreatment and dynamic BM T cell metrics proved to be better predictors of outcome than other established risk factors. The favorable broadening of the BM T cell space appeared to be driven by antigen since these patients showed significant skewing of TRBV gene usage. Our data suggest that one course of AZA can cause reconstitution to a more physiological T cell BM niche and that the T cell space plays an underestimated prognostic role in AML. |
URI: | https://opendata.uni-halle.de//handle/1981185920/87807 http://dx.doi.org/10.25673/85855 |
Open Access: | Open access publication |
License: | (CC BY 4.0) Creative Commons Attribution 4.0 |
Sponsor/Funder: | Publikationsfonds MLU |
Journal Title: | Blood cancer journal |
Publisher: | Nature Publishing Group |
Publisher Place: | London [u.a.] |
Volume: | 12 |
Original Publication: | 10.1038/s41408-022-00615-7 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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s41408-022-00615-7.pdf | 2.73 MB | Adobe PDF | View/Open |