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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number6263
JournalCancers
Volume13
Issue number24
DOIs
StatePublished - Dec 1 2021

Keywords

  • CML CD34+ cells
  • Pediatric CML
  • RNA sequencing
  • Rho pathway
  • Transcriptome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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