Comparison of the Transcriptomic Signatures in Pediatric and Adult CML

被引：12

作者：

Youn, Minyoung ^{[1
]}

Smith, Stephanie M. ^{[1
,2
]}

Lee, Alex Gia

Chae, Hee-Don ^{[1
]}

Spiteri, Elizabeth ^{[3
,4
]}

Erdmann, Jason ^{[4
]}

Galperin, Ilana ^{[4
]}

Jones, Lara Murphy ^{[1
,5
]}

Donato, Michele ^{[5
,6
]}

Abidi, Parveen ^{[7
]}

Bittencourt, Henrique ^{[8
]}

Lacayo, Norman ^{[1
]}

Dahl, Gary ^{[1
]}

Aftandilian, Catherine ^{[1
]}

Davis, Kara L. ^{[1
]}

Matthews, Jairo A. ^{[9
]}

Kornblau, Steven M. ^{[9
]}

Huang, Min ^{[1
]}

Sumarsono, Nathan ^{[1
]}

Redell, Michele S. ^{[10
]}

Fu, Cecilia H. ^{[11
]}

Chen, I-Ming ^{[12
]}

Alonzo, Todd A. ^{[13
]}

Eklund, Elizabeth ^{[14
]}

Gotlib, Jason ^{[7
]}

Khatri, Purvesh ^{[5
,6
]}

Sweet-Cordero, E. Alejandro ^{[2
]}

Hijiya, Nobuko ^{[15
]}

Sakamoto, Kathleen M. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA

[2] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[3] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[4] Stanford Hlth Care, Cytogenet Lab, Stanford, CA 94304 USA

[5] Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

[6] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Div Hematol, Dept Med,Stanford Canc Inst, Stanford, CA 94305 USA

[8] CHU St Justine, Charles Bruneau Canc Ctr, Hematol Oncol Div, Montreal, PQ H3T 1C5, Canada

[9] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[10] Baylor Coll Med, Div Pediat Hematol Oncol, Houston, TX 77030 USA

[11] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA

[12] Univ New Mexico, Comprehens Canc Ctr, Dept Pathol, Albuquerque, NM 87102 USA

[13] Univ Southern Calif, Dept Prevent Med, Los Angeles, CA 90032 USA

[14] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[15] Columbia Univ, Irving Med Ctr, Dept Pediat, New York, NY 10032 USA

来源：

CANCERS | 2021年 / 13卷 / 24期

关键词：

pediatric CML; CML CD34+cells; RNA sequencing; transcriptome; Rho pathway; CHRONIC MYELOID-LEUKEMIA; BCR-ABL; ACTIVATION; DIAGNOSIS; DISEASE; STEM;

D O I：

10.3390/cancers13246263

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. 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.

引用

页数：8

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