Clonal selection in therapy-related myelodysplastic syndromes and acute myeloid leukemia under azacitidine treatment
| Autor: | Seongseok Yun, Bérangère Dadone-Montaudie, David A. Sallman, Rami S. Komrokji, Anne Calleja, Jean Michel Karsenti, Lauris Gastaud, Chimène Moreilhon, Najla Al Ali, Thomas Cluzeau, Lionel Mannone, Guillaume Robert, Patrick Auberger, Sophie Raynaud |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Male medicine.medical_specialty Antimetabolites Antineoplastic Myeloid Azacitidine Clonal Evolution 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine medicine Biomarkers Tumor Humans neoplasms Gene Aged Aged 80 and over business.industry Myelodysplastic syndromes Myeloid leukemia High-Throughput Nucleotide Sequencing Hematology General Medicine medicine.disease stomatognathic diseases Leukemia Myeloid Acute medicine.anatomical_structure Treatment Outcome Hypomethylating agent 030220 oncology & carcinogenesis Myelodysplastic Syndromes Mutation Female Bone marrow Clone (B-cell biology) business 030215 immunology medicine.drug |
| Zdroj: | European journal of haematologyREFERENCES. 104(5) |
| ISSN: | 1600-0609 |
| Popis: | Introduction Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) are defined as complications of previous cytotoxic therapy. Azacitidine (AZA), a hypomethylating agent, has showed activity in t-MDS/AML. Objectives We evaluated the clonal dynamics of AZA-treated t-MDS/AML. Methods We collected bone marrow samples, at diagnosis and during treatment, from AZA-treated t-MDS/AML patients. NGS on 19 myeloid genes was performed, and candidate mutations with a variant allele frequency >5% were selected. Results Seven t-AML and 12 t-MDS were included with median age of 71 (56-82) years old, median number of AZA cycles of 6 (1-15), and median overall survival (OS) of 14 (3-29) months. We observed correlation between AZA response and clonal selection. Decrease of TP53-mutated clone was correlated with response to AZA, confirming AZA efficacy in this subgroup. In some patients, emergence of mutations was correlated with progression or relapse without impact on OS. Clones with mutations in genes for DNA methylation regulation frequently occurred with other mutations and remained stable during AZA treatment, independent of AZA response. Conclusion We confirmed that the molecular complexity of t-MNs and that the follow-up of clonal selection during AZA treatment could be useful to define treatment combination. |
| Databáze: | OpenAIRE |
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