Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics
Acute myelogenous leukemia (AML) is an aggressive hematological malignancy. The pathophysiology of the disease depends on cytogenetic abnormalities, gene mutations, aberrant gene expressions, and altered epigenetic regulation. Although new pharmacological agents have emerged during the last years, t...
Main Author: | |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-07-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/9/7/1677 |
id |
doaj-adeee39bbbdd48f0bc74417f95169214 |
---|---|
record_format |
Article |
spelling |
doaj-adeee39bbbdd48f0bc74417f951692142020-11-25T03:48:26ZengMDPI AGCells2073-44092020-07-0191677167710.3390/cells9071677Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell TranscriptomicsHåkon Reikvam0Institute of Clinical Science, University of Bergen, 5020 Bergen, NorwayAcute myelogenous leukemia (AML) is an aggressive hematological malignancy. The pathophysiology of the disease depends on cytogenetic abnormalities, gene mutations, aberrant gene expressions, and altered epigenetic regulation. Although new pharmacological agents have emerged during the last years, the prognosis is still dismal and new therapeutic strategies are needed. The transcription factor nuclear factor-κB (NF-κB) is regarded a possible therapeutic target. In this study, we investigated the alterations in the global gene expression profile (GEP) in primary AML cells derived from 16 consecutive patients after exposure to the NF-κB inhibitor BMS-345541. We identified a profound and highly discriminative transcriptomic profile associated with NF-κB inhibition. Bioinformatical analyses identified cytokine/interleukin signaling, metabolic regulation, and nucleic acid binding/transcription among the major biological functions influenced by NF-κB inhibition. Furthermore, several key genes involved in leukemogenesis, among them <i>RUNX1</i> and <i>CEBPA</i>, in addition to <i>NFKB1</i> itself, were influenced by NF-κB inhibition. Finally, we identified a significant impact of NF-κB inhibition on the expression of genes included in a leukemic stem cell (LSC) signature, indicating possible targeting of LSCs. We conclude that NF-κB inhibition significantly altered the expression of genes central to the leukemic process.https://www.mdpi.com/2073-4409/9/7/1677acute myelogenous leukemianuclear factor-κBtranscriptomiccytokinesmetabolismimmune system |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Håkon Reikvam |
spellingShingle |
Håkon Reikvam Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics Cells acute myelogenous leukemia nuclear factor-κB transcriptomic cytokines metabolism immune system |
author_facet |
Håkon Reikvam |
author_sort |
Håkon Reikvam |
title |
Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics |
title_short |
Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics |
title_full |
Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics |
title_fullStr |
Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics |
title_full_unstemmed |
Inhibition of NF-κB Signaling Alters Acute Myelogenous Leukemia Cell Transcriptomics |
title_sort |
inhibition of nf-κb signaling alters acute myelogenous leukemia cell transcriptomics |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-07-01 |
description |
Acute myelogenous leukemia (AML) is an aggressive hematological malignancy. The pathophysiology of the disease depends on cytogenetic abnormalities, gene mutations, aberrant gene expressions, and altered epigenetic regulation. Although new pharmacological agents have emerged during the last years, the prognosis is still dismal and new therapeutic strategies are needed. The transcription factor nuclear factor-κB (NF-κB) is regarded a possible therapeutic target. In this study, we investigated the alterations in the global gene expression profile (GEP) in primary AML cells derived from 16 consecutive patients after exposure to the NF-κB inhibitor BMS-345541. We identified a profound and highly discriminative transcriptomic profile associated with NF-κB inhibition. Bioinformatical analyses identified cytokine/interleukin signaling, metabolic regulation, and nucleic acid binding/transcription among the major biological functions influenced by NF-κB inhibition. Furthermore, several key genes involved in leukemogenesis, among them <i>RUNX1</i> and <i>CEBPA</i>, in addition to <i>NFKB1</i> itself, were influenced by NF-κB inhibition. Finally, we identified a significant impact of NF-κB inhibition on the expression of genes included in a leukemic stem cell (LSC) signature, indicating possible targeting of LSCs. We conclude that NF-κB inhibition significantly altered the expression of genes central to the leukemic process. |
topic |
acute myelogenous leukemia nuclear factor-κB transcriptomic cytokines metabolism immune system |
url |
https://www.mdpi.com/2073-4409/9/7/1677 |
work_keys_str_mv |
AT hakonreikvam inhibitionofnfkbsignalingaltersacutemyelogenousleukemiacelltranscriptomics |
_version_ |
1724499129981206528 |