Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients

Vasiliki Chondrou; Petros Kolovos; Argyro Sgourou; Alexandra Kourakli; Alexia Pavlidaki; Vlasia Kastrinou; Anne John; Argiris Symeonidis; Bassam R. Ali; Adamantia Papachatzopoulou; Theodora Katsila; George P. Patrinos

doi:10.1186/s40246-017-0120-8

Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients

Vasiliki Chondrou, Petros Kolovos, Argyro Sgourou, Alexandra Kourakli, Alexia Pavlidaki, Vlasia Kastrinou, Anne John, Argiris Symeonidis, Bassam R. Ali, Adamantia Papachatzopoulou, Theodora Katsila, George P. Patrinos^*

^*Corresponding author af dette arbejde

6 Citationer (Scopus)

64 Downloads (Pure)

Abstract

Background: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.

Originalsprog	Engelsk
Artikelnummer	24
Tidsskrift	Human Genomics
Vol/bind	11
Udgave nummer	1
Antal sider	11
ISSN	1473-9542
DOI	https://doi.org/10.1186/s40246-017-0120-8
Status	Udgivet - 4 mar. 2017

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10.1186/s40246-017-0120-8Licens: CC BY

Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β -type hemoglobinopathy patientsForlagets udgivne version, 1,69 MBLicens: CC BY

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Citationsformater

Chondrou, V., Kolovos, P., Sgourou, A., Kourakli, A., Pavlidaki, A., Kastrinou, V., John, A., Symeonidis, A., Ali, B. R., Papachatzopoulou, A., Katsila, T., & Patrinos, G. P. (2017). Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients. Human Genomics, 11(1), [24]. https://doi.org/10.1186/s40246-017-0120-8

Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients. / Chondrou, Vasiliki; Kolovos, Petros; Sgourou, Argyro et al.

I: Human Genomics, Bind 11, Nr. 1, 24, 04.03.2017.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Chondrou, V, Kolovos, P, Sgourou, A, Kourakli, A, Pavlidaki, A, Kastrinou, V, John, A, Symeonidis, A, Ali, BR, Papachatzopoulou, A, Katsila, T & Patrinos, GP 2017, 'Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients', Human Genomics, bind 11, nr. 1, 24. https://doi.org/10.1186/s40246-017-0120-8

Chondrou V, Kolovos P, Sgourou A, Kourakli A, Pavlidaki A, Kastrinou V et al. Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients. Human Genomics. 2017 mar. 4;11(1):24. doi: 10.1186/s40246-017-0120-8

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title = "Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients",

abstract = "Background: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.",

keywords = "Beta-thalassemia, Biomarkers, Erythroid cell differentiation, Ontogenesis, Pharmacogenomics, Sickle cell disease, Transcriptomics, VEGFA",

author = "Vasiliki Chondrou and Petros Kolovos and Argyro Sgourou and Alexandra Kourakli and Alexia Pavlidaki and Vlasia Kastrinou and Anne John and Argiris Symeonidis and Ali, {Bassam R.} and Adamantia Papachatzopoulou and Theodora Katsila and Patrinos, {George P.}",

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AU - Chondrou, Vasiliki

AU - Kolovos, Petros

AU - Sgourou, Argyro

AU - Kourakli, Alexandra

AU - Pavlidaki, Alexia

AU - Kastrinou, Vlasia

AU - John, Anne

AU - Symeonidis, Argiris

AU - Ali, Bassam R.

AU - Papachatzopoulou, Adamantia

AU - Katsila, Theodora

AU - Patrinos, George P.

PY - 2017/3/4

Y1 - 2017/3/4

N2 - Background: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.

AB - Background: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.

KW - Beta-thalassemia

KW - Biomarkers

KW - Erythroid cell differentiation

KW - Ontogenesis

KW - Pharmacogenomics

KW - Sickle cell disease

KW - Transcriptomics

KW - VEGFA

U2 - 10.1186/s40246-017-0120-8

DO - 10.1186/s40246-017-0120-8

M3 - Journal article

C2 - 29061162

AN - SCOPUS:85032202990

SN - 1479-7364

VL - 11

JO - Human Genomics

JF - Human Genomics

IS - 1

M1 - 24

ER -