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
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
Cancers (Basel). 2021 Dec 14;13(24):6263. doi: 10.3390/cancers13246263.
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.
与成人慢性粒细胞白血病（CML）患者相比，儿童CML患者往往表现出更高的白细胞计数和更大的脾脏，这表明儿童和成人CML的生物学特性可能存在差异。为了研究儿童和成人CML是否具有独特的分子特征，我们研究了儿童和成人CML CD34+细胞以及健康儿童和成人CD34+对照细胞的转录组特征。使用高通量RNA测序，我们发现与健康儿童CD34+细胞相比，儿童CML CD34+细胞中有567个基因（207个上调和360个下调）差异表达。直接比较儿童和成人CML CD34+细胞，在儿童CML CD34+细胞中有398个基因（258个上调和140个下调）差异表达，其中包括许多Rho途径中的基因。使用RT-qPCR验证差异表达基因，与儿童CML CD34+细胞相比，VAV2和ARHGAP27在成人CML CD34+细胞中显著上调。与健康对照相比，NCF1、CYBB和S100A8在成人CML CD34+细胞中上调，但在儿童CML CD34+细胞中未上调。相反，与健康对照相比，DLC1在儿童CML CD34+细胞中显著上调，但在成人CML CD34+细胞中未上调。这些结果证明了儿童CML的独特分子特征，如Rho途径失调可能导致儿童和成人患者之间的临床差异。
