Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia

The expression of apoptosis-related <i>BCL2</i> family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 B...

Full description

Bibliographic Details
Main Authors: Luiza Handschuh, Pawel Wojciechowski, Maciej Kazmierczak, Krzysztof Lewandowski
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/13/3175
_version_ 1797528711186087936
author Luiza Handschuh
Pawel Wojciechowski
Maciej Kazmierczak
Krzysztof Lewandowski
author_facet Luiza Handschuh
Pawel Wojciechowski
Maciej Kazmierczak
Krzysztof Lewandowski
author_sort Luiza Handschuh
collection DOAJ
description The expression of apoptosis-related <i>BCL2</i> family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of <i>BCL2</i> family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in <i>BMF</i>, <i>BNIP1</i>, and <i>HRK</i> was statistically significant. In a group of patients resistant to chemotherapy, overexpression of <i>BCL2L1</i> was manifested. In agreement with the literature data, our results reveal that <i>BCL2L1</i> is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that <i>BCL2</i> family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some <i>BCL2</i> family members, in particular <i>BIK</i> and <i>BCL2L13</i>, were associated with poor outcome.
first_indexed 2024-03-10T10:03:16Z
format Article
id doaj.art-11e3246d0b70446ca6814babd7a5aeaf
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-10T10:03:16Z
publishDate 2021-06-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-11e3246d0b70446ca6814babd7a5aeaf2023-11-22T01:45:02ZengMDPI AGCancers2072-66942021-06-011313317510.3390/cancers13133175Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic LeukemiaLuiza Handschuh0Pawel Wojciechowski1Maciej Kazmierczak2Krzysztof Lewandowski3Laboratory of Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandLaboratory of Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandDepartment of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 60-569 Poznan, PolandDepartment of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 60-569 Poznan, PolandThe expression of apoptosis-related <i>BCL2</i> family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of <i>BCL2</i> family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in <i>BMF</i>, <i>BNIP1</i>, and <i>HRK</i> was statistically significant. In a group of patients resistant to chemotherapy, overexpression of <i>BCL2L1</i> was manifested. In agreement with the literature data, our results reveal that <i>BCL2L1</i> is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that <i>BCL2</i> family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some <i>BCL2</i> family members, in particular <i>BIK</i> and <i>BCL2L13</i>, were associated with poor outcome.https://www.mdpi.com/2072-6694/13/13/3175AML<i>BCL2</i> familyapoptosisgene expressionRNA-seqexome sequencing
spellingShingle Luiza Handschuh
Pawel Wojciechowski
Maciej Kazmierczak
Krzysztof Lewandowski
Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
Cancers
AML
<i>BCL2</i> family
apoptosis
gene expression
RNA-seq
exome sequencing
title Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
title_full Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
title_fullStr Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
title_full_unstemmed Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
title_short Transcript-Level Dysregulation of <i>BCL2</i> Family Genes in Acute Myeloblastic Leukemia
title_sort transcript level dysregulation of i bcl2 i family genes in acute myeloblastic leukemia
topic AML
<i>BCL2</i> family
apoptosis
gene expression
RNA-seq
exome sequencing
url https://www.mdpi.com/2072-6694/13/13/3175
work_keys_str_mv AT luizahandschuh transcriptleveldysregulationofibcl2ifamilygenesinacutemyeloblasticleukemia
AT pawelwojciechowski transcriptleveldysregulationofibcl2ifamilygenesinacutemyeloblasticleukemia
AT maciejkazmierczak transcriptleveldysregulationofibcl2ifamilygenesinacutemyeloblasticleukemia
AT krzysztoflewandowski transcriptleveldysregulationofibcl2ifamilygenesinacutemyeloblasticleukemia