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Impact of clinical features, cytogenetics, genetic mutations, and methylation dynamics of CDKN2B and DLC-1 promoters on treatment response to azacitidine
- Source :
- ANNALS OF HEMATOLOGY, r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA, instname, r-FISABIO. Repositorio Institucional de Producción Científica, r-FISABIO: Repositorio Institucional de Producción Científica, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
- Publication Year :
- 2020
- Publisher :
- SPRINGER, 2020.
-
Abstract
- Azacitidine (AZA) is a DNA hypomethylation agent administered in myeloid neoplasms; however, there is still a lack of established predictors of response. We studied 113 patients with myelodysplastic syndromes (n = 85) or acute myeloid leukemia (n = 28) who received AZA to assess the predictive value on response of clinical features, cytogenetics, and molecular markers. Overall, 46 patients (41%) responded to AZA. Platelet doubling after the first AZA cycle was associated with a better response (68% vs. 32% responders, P = 0.041). Co-occurrence of chromosome 7 abnormalities and 17p deletion was associated with a worse response (P = 0.039). Pre-treatment genetic mutations were detected in 98 patients (87%) and methylation of CDKN2B and DLC-1 promoters were detected in 50 (44%) and 37 patients (33%), respectively. Patients with SF3B1 mutations showed a better response to AZA (68% vs. 35% responders, P = 0.008). In contrast, subjects with mutations in transcription factors (RUNX1, SETBP1, NPM1) showed a worse response (20% vs. 47% responders, P = 0.014). DLC-1 methylation pre-treatment was associated with poor clinical features and its reduction post-treatment resulted in a better response to AZA in MDS patients (P = 0.037). In conclusion, we have identified several predictors of response to AZA that could help select the best candidates for this treatment.
- Subjects :
- Oncology
Male
medicine.medical_specialty
NPM1
Myeloid
Azacitidine
Myelodysplastic syndromes
Gene mutation
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Promoter Regions, Genetic
Aged
Cyclin-Dependent Kinase Inhibitor p15
Chromosome 7 (human)
Aged, 80 and over
Hematology
Acute myeloid leukemia
business.industry
Tumor Suppressor Proteins
GTPase-Activating Proteins
Myeloid leukemia
General Medicine
DNA, Neoplasm
DNA Methylation
Middle Aged
Platelet doubling
medicine.disease
Promoter methylation
Survival Rate
Leukemia, Myeloid, Acute
medicine.anatomical_structure
030220 oncology & carcinogenesis
Myelodysplastic Syndromes
Gene mutations
Female
Chromosome Deletion
business
Nucleophosmin
Chromosomes, Human, Pair 7
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 09395555
- Database :
- OpenAIRE
- Journal :
- ANNALS OF HEMATOLOGY, r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA, instname, r-FISABIO. Repositorio Institucional de Producción Científica, r-FISABIO: Repositorio Institucional de Producción Científica, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
- Accession number :
- edsair.doi.dedup.....68b3ec181c4ef6316cf42315cf1c63bf