Minyoung Youn, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Stephanie M. Smith, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Alex Gia Lee, Department of Pediatrics, University of California, San Francisco, CA 94143, USA
Hee-Don Chae, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Elizabeth Spiteri, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Cytogenetics Laboratory, Stanford Health Care, Stanford, CA 94304, USA
Jason Erdmann, Cytogenetics Laboratory, Stanford Health Care, Stanford, CA 94304, USA
Ilana Galperin, Cytogenetics Laboratory, Stanford Health Care, Stanford, CA 94304, USA
Lara Murphy Jones, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA
Michele Donato, Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA 94305, USA
Parveen Abidi, Division of Hematology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
Henrique Bittencourt, Hematology-Oncology Division, Charles Bruneau Cancer Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC H3T 1C5, Canada
Norman Lacayo, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Gary Dahl, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Catherine Aftandilian, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Kara L. Davis, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Jairo A. Matthews, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Steven M. Kornblau, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Min Huang, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Nathan Sumarsono, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Michele S. Redell, Division of Pediatric Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA
Cecilia H. Fu, Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA
I-Ming Chen, Department of Pathology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87102, USA
Todd A. Alonzo, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90032, USA
Elizabeth Eklund, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Jason Gotlib, Division of Hematology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
Purvesh Khatri, Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA 94305, USA
E Alejandro Sweet-Cordero, Department of Pediatrics, University of California, San Francisco, CA 94143, USA
Nobuko Hijiya, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA
Kathleen M. Sakamoto, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA

Document Type

Article

Publication Date

12-14-2021

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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