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Detection and Targeting of Splicing Deregulation in Pediatric Acute Myeloid Leukemia Stem Cells
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Catriona Jamieson, PhD, MD,  
Project

About This Dataset
This study evaluates the gene expression and splicing changes between pediatric patients with and without Acute Myeloid Leukemia (AML) and pediatric and adult patients with AML. We obtained bone marrow or peripheral blood from patients and isolated CD34+ stem and/or progenitor cells from pediatric patients with AML (10) or without AML (6) and adult patients with AML (5). In parallel, a targeted analysis for known, deleterious, genetic mutations in the KRAS, NRAS, and KMT2C genes identified 2, 5, and 6 AML patients with alterations, respectively. Additionally, Tapestri analysis further identified a mutation in the intronic region of the SF3B1 gene in multiple pediatric AML patients. RNA-Seq was performed on the purified cell populations at The Scripps Research Institute Next Generation Core on an Illumina NextSeq 500 sequencer with 150bp paired-end reads. These datasets revealed that, similar to adult AML, pediatric AML samples were enriched for Leukemia Stem Cells (LSC) markers. A deeper analysis showed widespread dysregulation of splicing in pediatric AML samples compared to age-matched non-leukemic samples. In addition, the splicing regulator RBFOX2 was downregulated with an accompanying increase in specific CD47 splice isoforms in the pediatric AML samples. Thus, the increased presence of LSCs in pediatric AML is possibly driven by global splicing deregulation, and the treatment with splicing modulators like Rebecsinib has a potential therapeutic value for eradicating LSCs in these patients.
Core Data Elements
Number of Cases
21
Case Sex
Female (7); Male (14)
Case Age At Diagnosis
0 to 4 years (5); 5 to 9 years (6); 10 to 14 years (5); 30 to 34 years (1); Greater than 39 years (4)
Case Race
Not Reported (21)
Case Ethnicity
Not Reported (21)
Case Disease Diagnosis
Acute Myeloid Leukemia (21)
Number of Samples
36
Sample Analyte Type
RNA (36)
Sample Anatomic Site
Bone Marrow (21); Peripheral Blood (15)
Sample Is Normal
Yes (9); No (27)
Additional Data Elements
DBGAP STUDY IDENTIFIER
Grant Information
R01CA205944
Characterization of the Role of ADAR1 in Oncogenic Transformation of Progenitors
R01DK114468-01
Defining the Niche-dependent Role of RNA Editing in Aged and MDS Hematopoietic Stem and Progenitor Cell Dysfunction
Published In
https://doi.org/10.1016/j.stem.2016.08.003
Charts
Male (14); Female (7)
14Male