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RNA-Sequencing of B-Lymphoblastic Leukemia with Glucocorticoids and PI3K Delta Inhibition
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Miles A. Pufall, PhD,  
Project

About This Dataset
Mononuclear cells were isolated from bone marrow or peripheral blood of 7 pediatric subjects with B-lymphoblastic leukemia at the time of diagnosis. To determine the effect of PI3K delta inhibition on glucocorticoid-induced gene regulation, B-lymphoblastic leukemia cells were treated with glucocorticoids +/- the PI3K delta inhibitor, idelalisib, for 24 hours prior to RNA extraction and sequencing. Biological replicates were performed for 4 of the 7 subjects; 2 of these subjects had specimens demonstrating an additive response to the combination of glucocorticoids and idelalisib in viability testing in vitro, and 2 subjects' specimens demonstrated a synergistic response. All 7 subjects were analyzed together and the 4 specimens with biological replicates were also evaluated in an additional analysis. An average of 40 million reads per specimen and treatment condition were obtained. We compared gene expression in each treatment condition to vehicle-treated cells and expression in glucocorticoid or idelalisib only treated cells to combination treated cells. Using a high dose of dexamethasone (25 or 50 nM) and an equivalent dose of prednisolone, we found that the addition of idelalisib (500 nM) enhanced prednisolone-induced gene regulation but not dexamethasone-induced gene regulation. Surprisingly, the specimens with additive response to combination therapy demonstrated enhancement of prednisolone-induced gene regulation with the addition of idelalisib, while the specimens with synergistic responses did not. Raw sequencing data (FASTQ) and count tables will be available through dbGaP.
Core Data Elements
Number of Cases
7
Case Sex
Female (1); Male (6)
Case Age At Diagnosis
0 to 4 years (3); 5 to 9 years (2); 10 to 14 years (1); 15 to 19 years (1)
Case Race
Not Reported (7)
Case Ethnicity
Not Reported (7)
Case Disease Diagnosis
B-Lymphoblastic Leukemia (7)
Number of Samples
65
Sample Analyte Type
RNA (65)
Sample Anatomic Site
Bone Marrow (42); Peripheral Blood (23)
Additional Data Elements
DBGAP STUDY IDENTIFIER
Grant Information
P30CA086862
Cancer Center Support Grant
Charts
Male (6); Female (1)
6Male