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Comparison of the Transcriptomic Signatures in Pediatric and Adult CML

SIMPLE SUMMARY: To investigate whether pediatric and adult chronic myeloid leukemia (CML) have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML cells using high-throughput RNA sequencing. We identified differentially expressed genes and pathways un...

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Autores principales: Youn, Minyoung, Smith, Stephanie M., Lee, Alex Gia, Chae, Hee-Don, Spiteri, Elizabeth, Erdmann, Jason, Galperin, Ilana, Jones, Lara Murphy, Donato, Michele, Abidi, Parveen, Bittencourt, Henrique, Lacayo, Norman, Dahl, Gary, Aftandilian, Catherine, Davis, Kara L., Matthews, Jairo A., Kornblau, Steven M., Huang, Min, Sumarsono, Nathan, Redell, Michele S., Fu, Cecilia H., Chen, I-Ming, Alonzo, Todd A., Eklund, Elizabeth, Gotlib, Jason, Khatri, Purvesh, Sweet-Cordero, E. Alejandro, Hijiya, Nobuko, Sakamoto, Kathleen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699058/
https://www.ncbi.nlm.nih.gov/pubmed/34944883
http://dx.doi.org/10.3390/cancers13246263
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author Youn, Minyoung
Smith, Stephanie M.
Lee, Alex Gia
Chae, Hee-Don
Spiteri, Elizabeth
Erdmann, Jason
Galperin, Ilana
Jones, Lara Murphy
Donato, Michele
Abidi, Parveen
Bittencourt, Henrique
Lacayo, Norman
Dahl, Gary
Aftandilian, Catherine
Davis, Kara L.
Matthews, Jairo A.
Kornblau, Steven M.
Huang, Min
Sumarsono, Nathan
Redell, Michele S.
Fu, Cecilia H.
Chen, I-Ming
Alonzo, Todd A.
Eklund, Elizabeth
Gotlib, Jason
Khatri, Purvesh
Sweet-Cordero, E. Alejandro
Hijiya, Nobuko
Sakamoto, Kathleen M.
author_facet Youn, Minyoung
Smith, Stephanie M.
Lee, Alex Gia
Chae, Hee-Don
Spiteri, Elizabeth
Erdmann, Jason
Galperin, Ilana
Jones, Lara Murphy
Donato, Michele
Abidi, Parveen
Bittencourt, Henrique
Lacayo, Norman
Dahl, Gary
Aftandilian, Catherine
Davis, Kara L.
Matthews, Jairo A.
Kornblau, Steven M.
Huang, Min
Sumarsono, Nathan
Redell, Michele S.
Fu, Cecilia H.
Chen, I-Ming
Alonzo, Todd A.
Eklund, Elizabeth
Gotlib, Jason
Khatri, Purvesh
Sweet-Cordero, E. Alejandro
Hijiya, Nobuko
Sakamoto, Kathleen M.
author_sort Youn, Minyoung
collection PubMed
description SIMPLE SUMMARY: To investigate whether pediatric and adult chronic myeloid leukemia (CML) have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML cells using high-throughput RNA sequencing. We identified differentially expressed genes and pathways unique to pediatric CML cells compared to adult CML cells. The Rho pathway was significantly dysregulated in pediatric CML cells compared to adult CML cells, suggesting the potential importance in the pathogenesis of pediatric CML. Our study is the first to compare transcriptome profiles of CML across different age groups. A better understanding of the biology of CML across different ages may inform future treatment approaches. ABSTRACT: Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.
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spelling pubmed-86990582021-12-24 Comparison of the Transcriptomic Signatures in Pediatric and Adult CML Youn, Minyoung Smith, Stephanie M. Lee, Alex Gia Chae, Hee-Don Spiteri, Elizabeth Erdmann, Jason Galperin, Ilana Jones, Lara Murphy Donato, Michele Abidi, Parveen Bittencourt, Henrique Lacayo, Norman Dahl, Gary Aftandilian, Catherine Davis, Kara L. Matthews, Jairo A. Kornblau, Steven M. Huang, Min Sumarsono, Nathan Redell, Michele S. Fu, Cecilia H. Chen, I-Ming Alonzo, Todd A. Eklund, Elizabeth Gotlib, Jason Khatri, Purvesh Sweet-Cordero, E. Alejandro Hijiya, Nobuko Sakamoto, Kathleen M. Cancers (Basel) Communication SIMPLE SUMMARY: To investigate whether pediatric and adult chronic myeloid leukemia (CML) have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML cells using high-throughput RNA sequencing. We identified differentially expressed genes and pathways unique to pediatric CML cells compared to adult CML cells. The Rho pathway was significantly dysregulated in pediatric CML cells compared to adult CML cells, suggesting the potential importance in the pathogenesis of pediatric CML. Our study is the first to compare transcriptome profiles of CML across different age groups. A better understanding of the biology of CML across different ages may inform future treatment approaches. ABSTRACT: Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients. MDPI 2021-12-14 /pmc/articles/PMC8699058/ /pubmed/34944883 http://dx.doi.org/10.3390/cancers13246263 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Youn, Minyoung
Smith, Stephanie M.
Lee, Alex Gia
Chae, Hee-Don
Spiteri, Elizabeth
Erdmann, Jason
Galperin, Ilana
Jones, Lara Murphy
Donato, Michele
Abidi, Parveen
Bittencourt, Henrique
Lacayo, Norman
Dahl, Gary
Aftandilian, Catherine
Davis, Kara L.
Matthews, Jairo A.
Kornblau, Steven M.
Huang, Min
Sumarsono, Nathan
Redell, Michele S.
Fu, Cecilia H.
Chen, I-Ming
Alonzo, Todd A.
Eklund, Elizabeth
Gotlib, Jason
Khatri, Purvesh
Sweet-Cordero, E. Alejandro
Hijiya, Nobuko
Sakamoto, Kathleen M.
Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title_full Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title_fullStr Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title_full_unstemmed Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title_short Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
title_sort comparison of the transcriptomic signatures in pediatric and adult cml
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699058/
https://www.ncbi.nlm.nih.gov/pubmed/34944883
http://dx.doi.org/10.3390/cancers13246263
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