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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.

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.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Martín I,Navarro B,Serrano A,Villamón E,Calabuig M,Solano C,Chaves FJ,Yagüe N,Orts M,Amat P,Fuentes A,Seda E,García F,Hernández-Boluda JC,Tormo M

doi

10.1007/s00277-020-03932-8

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

527-537

issue

3

eissn

0939-5555

issn

1432-0584

pii

10.1007/s00277-020-03932-8

journal_volume

99

pub_type

临床试验,杂志文章

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