Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selection in patients-responders

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F17%3A10366073" target="_blank" >RIV/00216208:11320/17:10366073 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/17:10366073 RIV/00064165:_____/17:10366073

Result on the web

<a href="https://doi.org/10.18632/oncotarget.22957" target="_blank" >https://doi.org/10.18632/oncotarget.22957</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.22957" target="_blank" >10.18632/oncotarget.22957</a>

Result language

angličtina

Original language name

Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selection in patients-responders

Original language description

Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited durability. To monitor mutation dynamics during AZA therapy we utilized massive parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis. Serial sampling before and during AZA therapy of 38 patients (reaching median overall survival 24 months (Mo) with 60% clinical responses) identified 116 somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High accuracy of data was achieved via duplicate libraries from myeloid cells and T-cell controls. We observed that nearly half of the variants were stable while other variants were highly dynamic. Patients with marked decrease of allelic burden upon AZA therapy achieved clinical responses. In contrast, early-progressing patients on AZA displayed minimal changes of the mutation pattern. We modeled the VAF dynamics on AZA and utilized a joint model for the overall survival and response duration. While the presence of certain variants associated with clinical outcomes, such as the mutations of CDKN2A were adverse predictors while KDM6A mutations yield lower risk of dying, the data also indicate that allelic burden volatility represents additional important prognostic variable. In addition, preceding 5q- syndrome represents strong positive predictor of longer overall survival and response duration in high risk MDS patients treated with AZA. In conclusion, variants dynamics detected via serial sampling represents another parameter to consider when evaluating AZA efficacy and predicting outcome.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30205 - Hematology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Oncotarget

ISSN

1949-2553

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

67

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

111966-111978

UT code for WoS article

000419567000097

EID of the result in the Scopus database

2-s2.0-85038426988