Low plasma citrate levels and specific transcriptional signatures associated with quiescence of CD34+ progenitors predict Azacitidine therapy failure in MDS/AML patients
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023736%3A_____%2F21%3A00013232" target="_blank" >RIV/00023736:_____/21:00013232 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/21:10428898 RIV/00064165:_____/21:10428898 RIV/61989592:15110/21:73610138
Result on the web
<a href="https://doi.org/10.3390/cancers13092161" target="_blank" >https://doi.org/10.3390/cancers13092161</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cancers13092161" target="_blank" >10.3390/cancers13092161</a>
Alternative languages
Result language
angličtina
Original language name
Low plasma citrate levels and specific transcriptional signatures associated with quiescence of CD34+ progenitors predict Azacitidine therapy failure in MDS/AML patients
Original language description
To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients of the discovery cohort (10 AZA responders (RD), six stable disease, nine progressive disease (PD) during AZA therapy) and from eight controls. Eleven MDS/AML-MRC samples were also available for analysis of selected metabolites, along with 17 additional samples from an independent validation cohort. Except for two patients, the others did not carry isocitrate dehydrogenase (IDH)1/2 mutations. Transcriptional landscapes of the patients’ HSPCs were comparable to those published previously, including decreased signatures of active cell cycling and DNA damage response in PD compared to RD and controls. In addition, PD-derived HSPCs revealed repressed markers of the tricarboxylic acid cycle, with IDH2 among the top 50 downregulated genes in PD compared to RD. Decreased citrate plasma levels, downregulated expression of the (ATP)-citrate lyase and other transcriptional/metabolic networks indicate metabolism-driven histone modifications in PD HSPCs. Observed histone deacetylation is consistent with transcription-nonpermissive chromatin configuration and quiescence of PD HSPCs. This study highlights the complexity of the molecular network underlying response/resistance to hypomethylating agents.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/NV16-33485A" target="_blank" >NV16-33485A: Integrative analysis of genomic changes in DNA repair systems in myelodysplastic syndrome and their relevance in the pathogenesis</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancers
ISSN
2072-6694
e-ISSN
—
Volume of the periodical
13
Issue of the periodical within the volume
9
Country of publishing house
CH - SWITZERLAND
Number of pages
21
Pages from-to
"art. no. 2161"
UT code for WoS article
000649890400001
EID of the result in the Scopus database
2-s2.0-85117430069