Comparison of the transcriptomic signatures in pediatric and adult CML

Minyoung Youn; Stephanie M. Smith; Alex Gia Lee; Hee Don Chae; Elizabeth Spiteri; Jason Erdmann; Ilana Galperin; Lara Murphy Jones; Michele Donato; Parveen Abidi; Henrique Bittencourt; Norman Lacayo; Gary Dahl; Catherine Aftandilian; Kara L. Davis; Jairo A. Matthews; Steven M. Kornblau; Min Huang; Nathan Sumarsono; Michele S. Redell; Cecilia H. Fu; I. Ming Chen; Todd A. Alonzo; Elizabeth Eklund; Jason Gotlib; Purvesh Khatri; E. Alejandro Sweet-Cordero; Nobuko Hijiya; Kathleen M. Sakamoto

doi:10.3390/cancers13246263

Comparison of the transcriptomic signatures in pediatric and adult CML

Minyoung Youn, Stephanie M. Smith, Alex Gia Lee, Hee Don Chae, Elizabeth Spiteri, Jason Erdmann, Ilana Galperin, Lara Murphy Jones, Michele Donato, Parveen Abidi, Henrique Bittencourt, Norman Lacayo, Gary Dahl, Catherine Aftandilian, Kara L. Davis, Jairo A. Matthews, Steven M. Kornblau, Min Huang, Nathan Sumarsono, Michele S. RedellCecilia H. Fu, I. Ming Chen, Todd A. Alonzo, Elizabeth Eklund, Jason Gotlib, Purvesh Khatri, E. Alejandro Sweet-Cordero, Nobuko Hijiya, Kathleen M. Sakamoto

Leukemia

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Article number	6263
Journal	Cancers
Volume	13
Issue number	24
DOIs	https://doi.org/10.3390/cancers13246263
State	Published - Dec 1 2021

Keywords

CML CD34+ cells
Pediatric CML
RNA sequencing
Rho pathway
Transcriptome

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.3390/cancers13246263

Cite this

Youn, M., Smith, S. M., Lee, A. G., Chae, H. D., Spiteri, E., Erdmann, J., Galperin, I., Jones, L. M., Donato, M., Abidi, P., Bittencourt, H., Lacayo, N., Dahl, G., Aftandilian, C., Davis, K. L., Matthews, J. A., Kornblau, S. M., Huang, M., Sumarsono, N., ... Sakamoto, K. M. (2021). Comparison of the transcriptomic signatures in pediatric and adult CML. Cancers, 13(24), Article 6263. https://doi.org/10.3390/cancers13246263

Youn, M, Smith, SM, Lee, AG, Chae, HD, Spiteri, E, Erdmann, J, Galperin, I, Jones, LM, Donato, M, Abidi, P, Bittencourt, H, Lacayo, N, Dahl, G, Aftandilian, C, Davis, KL, Matthews, JA, Kornblau, SM, Huang, M, Sumarsono, N, Redell, MS, Fu, CH, Chen, IM, Alonzo, TA, Eklund, E, Gotlib, J, Khatri, P, Sweet-Cordero, EA, Hijiya, N & Sakamoto, KM 2021, 'Comparison of the transcriptomic signatures in pediatric and adult CML', Cancers, vol. 13, no. 24, 6263. https://doi.org/10.3390/cancers13246263

@article{acb7785167d04607a50540d56a6e8e4b,

title = "Comparison of the transcriptomic signatures in pediatric and adult CML",

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.",

keywords = "CML CD34+ cells, Pediatric CML, RNA sequencing, Rho pathway, Transcriptome",

author = "Minyoung Youn and Smith, {Stephanie M.} and Lee, {Alex Gia} and Chae, {Hee Don} and Elizabeth Spiteri and Jason Erdmann and Ilana Galperin and Jones, {Lara Murphy} and Michele Donato and Parveen Abidi and Henrique Bittencourt and Norman Lacayo and Gary Dahl and Catherine Aftandilian and Davis, {Kara L.} and Matthews, {Jairo A.} and Kornblau, {Steven M.} and Min Huang and Nathan Sumarsono and Redell, {Michele S.} and Fu, {Cecilia H.} and Chen, {I. Ming} and Alonzo, {Todd A.} and Elizabeth Eklund and Jason Gotlib and Purvesh Khatri and Sweet-Cordero, {E. Alejandro} and Nobuko Hijiya and Sakamoto, {Kathleen M.}",

note = "Funding Information: Funding: This work was supported by the Stanford Maternal Child Health Research Institute and Lurie Children{\textquoteright}s Hospital/Northwestern University. This research received no external funding. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = dec,

day = "1",

doi = "10.3390/cancers13246263",

language = "English (US)",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "24",

}

TY - JOUR

T1 - Comparison of the transcriptomic signatures in pediatric and adult CML

AU - Youn, Minyoung

AU - Smith, Stephanie M.

AU - Lee, Alex Gia

AU - Chae, Hee Don

AU - Spiteri, Elizabeth

AU - Erdmann, Jason

AU - Galperin, Ilana

AU - Jones, Lara Murphy

AU - Donato, Michele

AU - Abidi, Parveen

AU - Bittencourt, Henrique

AU - Lacayo, Norman

AU - Dahl, Gary

AU - Aftandilian, Catherine

AU - Davis, Kara L.

AU - Matthews, Jairo A.

AU - Kornblau, Steven M.

AU - Huang, Min

AU - Sumarsono, Nathan

AU - Redell, Michele S.

AU - Fu, Cecilia H.

AU - Chen, I. Ming

AU - Alonzo, Todd A.

AU - Eklund, Elizabeth

AU - Gotlib, Jason

AU - Khatri, Purvesh

AU - Sweet-Cordero, E. Alejandro

AU - Hijiya, Nobuko

AU - Sakamoto, Kathleen M.

N1 - Funding Information: Funding: This work was supported by the Stanford Maternal Child Health Research Institute and Lurie Children’s Hospital/Northwestern University. This research received no external funding. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - CML CD34+ cells

KW - Pediatric CML

KW - RNA sequencing

KW - Rho pathway

KW - Transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85121419584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85121419584&partnerID=8YFLogxK

U2 - 10.3390/cancers13246263

DO - 10.3390/cancers13246263

M3 - Article

C2 - 34944883

AN - SCOPUS:85121419584

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 24

M1 - 6263

ER -

Comparison of the transcriptomic signatures in pediatric and adult CML

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this