BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023736%3A_____%2F18%3A00012154" target="_blank" >RIV/00023736:_____/18:00012154 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/18:10385555

Výsledek na webu

<a href="https://doi.org/10.3324/haematol.2018.193086" target="_blank" >https://doi.org/10.3324/haematol.2018.193086</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2018.193086" target="_blank" >10.3324/haematol.2018.193086</a>

Jazyk výsledku

angličtina

Název v původním jazyce

BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia

Popis výsledku v původním jazyce

The fusion oncoprotein BCR-ABL1 exhibits aberrant tyrosine kinase activity and has been proposed to deregulate signaling networks involving both transcription factors and non-coding microRNAs that result in chronic myeloid leukemia. Previously, microRNA expression profiling showed deregulated expression of miR-150 and miR-155 in chronic myeloid leukemia. In this study, we placed these findings into the broader context of the MYC/miR-150/MYB/miR-155/PU.1 oncogenic network. We propose that upregulated MYC and miR-155 in CD34+ leukemic stem and progenitor cells in concert with BCR-ABL1 impair the molecular mechanisms of myeloid differentiation associated with low miR-150 and PU.1 levels. We revealed that MYC directly occupied the -11.7 kb and -0.35 kb regulatory regions in the MIR150 gene. MYC occupancy was markedly increased through BCR-ABL1 activity, causing inhibition of MIR150 gene expression in chronic myeloid leukemia CD34+ and CD34- cells

Název v anglickém jazyce

BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia

Popis výsledku anglicky

The fusion oncoprotein BCR-ABL1 exhibits aberrant tyrosine kinase activity and has been proposed to deregulate signaling networks involving both transcription factors and non-coding microRNAs that result in chronic myeloid leukemia. Previously, microRNA expression profiling showed deregulated expression of miR-150 and miR-155 in chronic myeloid leukemia. In this study, we placed these findings into the broader context of the MYC/miR-150/MYB/miR-155/PU.1 oncogenic network. We propose that upregulated MYC and miR-155 in CD34+ leukemic stem and progenitor cells in concert with BCR-ABL1 impair the molecular mechanisms of myeloid differentiation associated with low miR-150 and PU.1 levels. We revealed that MYC directly occupied the -11.7 kb and -0.35 kb regulatory regions in the MIR150 gene. MYC occupancy was markedly increased through BCR-ABL1 activity, causing inhibition of MIR150 gene expression in chronic myeloid leukemia CD34+ and CD34- cells

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/LH15104" target="_blank" >LH15104: Studium epigenetických faktorů a tumor-supresorových genů regulujících onkogenní signální dráhy na modelech leukemické hematopoézy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Haematologica

ISSN

0390-6078

e-ISSN

—

Svazek periodika

103

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

IT - Italská republika

Počet stran výsledku

10

Strana od-do

2016-2025

Kód UT WoS článku

000451736600026

EID výsledku v databázi Scopus

2-s2.0-85060844821