Heterogeneous genetic and non‐genetic mechanisms contribute to response and resistance to azacitidine monotherapy
| Title: | Heterogeneous genetic and non‐genetic mechanisms contribute to response and resistance to azacitidine monotherapy |
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| Authors: | Vasiliki Symeonidou, Marlen Metzner, Batchimeg Usukhbayar, Aimee E. Jackson, Sonia Fox, Charles F. Craddock, Paresh Vyas |
| Source: | eJHaem, Vol 3, Iss 3, Pp 794-803 (2022) |
| Publisher Information: | Wiley, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Diseases of the blood and blood-forming organs |
| Subject Terms: | acute myeloid leukaemia, azacitidine, clonal evolution, hypomethylating agents, immune microenvironment, Diseases of the blood and blood-forming organs, RC633-647.5 |
| More Details: | Abstract Acute myeloid leukaemia is prevalent in older patients that are often ineligible for intensive chemotherapy and treatment options remain limited with azacitidine being at the forefront. Azacitidine has been used in the clinic for decades, however, we still lack a complete understanding of the mechanisms by which the drug exerts its anti‐tumour effect. To gain insight into the mechanism of action, we defined the mutational profile of sequential samples of patients treated with azacitidine. We did not identify any mutations that could predict response and observed lack of a uniform pattern of clonal evolution. Focusing on responders, at remission, we observed three types of response: (1) an almost complete elimination of mutations (33%), (2) no change (17%), and (3) change with no discernible pattern (50%). Heterogeneous patterns were also observed at relapse, with no clonal evolution between remission and relapse in some patients. Lack of clonal evolution suggests that non‐genetic mechanisms might be involved. Towards understanding such mechanisms, we investigated the immune microenvironment in a number of patients and we observed lack of a uniform response following therapy. We identified a higher frequency of cytotoxic T cells in responders and higher frequency of naïve helper T cells in non‐responders. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2688-6146 63341778 |
| Relation: | https://doaj.org/toc/2688-6146 |
| DOI: | 10.1002/jha2.527 |
| Access URL: | https://doaj.org/article/0ec7692b03e049f3a63341778660afdb |
| Accession Number: | edsdoj.0ec7692b03e049f3a63341778660afdb |
| Database: | Directory of Open Access Journals |
| ISSN: | 26886146 63341778 |
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| DOI: | 10.1002/jha2.527 |
| Published in: | eJHaem |
| Language: | English |