Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous disease. A significant proportion of AML patients is refractory to clinical treatment or relapses. Our aim is to determine new potential AML clinical treatment prognosis markers. We investigated various cell fate and epigenetic regulation important gen...

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Main Authors: Aida Vitkevičienė, Giedrė Skliutė, Andrius Žučenka, Veronika Borutinskaitė, Rūta Navakauskienė
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/11/2752
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author Aida Vitkevičienė
Giedrė Skliutė
Andrius Žučenka
Veronika Borutinskaitė
Rūta Navakauskienė
author_facet Aida Vitkevičienė
Giedrė Skliutė
Andrius Žučenka
Veronika Borutinskaitė
Rūta Navakauskienė
author_sort Aida Vitkevičienė
collection DOAJ
description Acute myeloid leukemia (AML) is a heterogeneous disease. A significant proportion of AML patients is refractory to clinical treatment or relapses. Our aim is to determine new potential AML clinical treatment prognosis markers. We investigated various cell fate and epigenetic regulation important gene level differences between refractory and responsive AML patient groups at diagnosis stage and after clinical treatment using RT-qPCR. We demonstrated that oncogenic <i>MYC</i> and <i>WT1</i> and metabolic <i>IDH1</i> gene expression was significantly higher and cell cycle inhibitor <i>CDKN1A (p21)</i> gene expression was significantly lower in refractory patients’ bone marrow cells compared to treatment responsive patients both at diagnosis and after clinical treatment. Moreover, we determined that, compared to clinical treatment responsive patients, refractory patients possess a significantly higher gene expression of histone deacetylase 2 (<i>HDAC2</i>) and epigenetic DNA modulator <i>TET1</i> and a significantly lower gene expression of lysine acetyltransferase 6A (<i>KAT6A</i>) and nucleosome remodeling and deacetylase (NuRD) complex component <i>GATAD2A</i>. We suggest that <i>MYC</i>, <i>WT1</i>, <i>IDH1</i>, <i>CDKN1A</i>, <i>HDAC2</i>, <i>TET1</i>, <i>KAT6A</i> and <i>GATAD2A</i> gene expression changes might characterize refractory AML. Thus, they might be useful for AML prognosis. Additionally, we suggest that epigenetic modulation might be beneficial in combination with standard treatment.
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spelling doaj.art-18b73d850d544fc98b4b5d1f2be4ae8b2023-11-23T13:50:33ZengMDPI AGCancers2072-66942022-06-011411275210.3390/cancers14112752Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid LeukemiaAida Vitkevičienė0Giedrė Skliutė1Andrius Žučenka2Veronika Borutinskaitė3Rūta Navakauskienė4Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-01257 Vilnius, LithuaniaDepartment of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-01257 Vilnius, LithuaniaHematology, Oncology and Transfusion Medicine Centre, Vilnius University Hospital Santaros Klinikos, Santariskiu str. 2, LT-08661 Vilnius, LithuaniaDepartment of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-01257 Vilnius, LithuaniaDepartment of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-01257 Vilnius, LithuaniaAcute myeloid leukemia (AML) is a heterogeneous disease. A significant proportion of AML patients is refractory to clinical treatment or relapses. Our aim is to determine new potential AML clinical treatment prognosis markers. We investigated various cell fate and epigenetic regulation important gene level differences between refractory and responsive AML patient groups at diagnosis stage and after clinical treatment using RT-qPCR. We demonstrated that oncogenic <i>MYC</i> and <i>WT1</i> and metabolic <i>IDH1</i> gene expression was significantly higher and cell cycle inhibitor <i>CDKN1A (p21)</i> gene expression was significantly lower in refractory patients’ bone marrow cells compared to treatment responsive patients both at diagnosis and after clinical treatment. Moreover, we determined that, compared to clinical treatment responsive patients, refractory patients possess a significantly higher gene expression of histone deacetylase 2 (<i>HDAC2</i>) and epigenetic DNA modulator <i>TET1</i> and a significantly lower gene expression of lysine acetyltransferase 6A (<i>KAT6A</i>) and nucleosome remodeling and deacetylase (NuRD) complex component <i>GATAD2A</i>. We suggest that <i>MYC</i>, <i>WT1</i>, <i>IDH1</i>, <i>CDKN1A</i>, <i>HDAC2</i>, <i>TET1</i>, <i>KAT6A</i> and <i>GATAD2A</i> gene expression changes might characterize refractory AML. Thus, they might be useful for AML prognosis. Additionally, we suggest that epigenetic modulation might be beneficial in combination with standard treatment.https://www.mdpi.com/2072-6694/14/11/2752acute myeloid leukemia (AML)prognostic markersepigenetic regulation
spellingShingle Aida Vitkevičienė
Giedrė Skliutė
Andrius Žučenka
Veronika Borutinskaitė
Rūta Navakauskienė
Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
Cancers
acute myeloid leukemia (AML)
prognostic markers
epigenetic regulation
title Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
title_full Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
title_fullStr Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
title_full_unstemmed Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
title_short Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
title_sort potential prognostic markers for relapsed refractory vs responsive acute myeloid leukemia
topic acute myeloid leukemia (AML)
prognostic markers
epigenetic regulation
url https://www.mdpi.com/2072-6694/14/11/2752
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