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Series GSE150784 Query DataSets for GSE150784
Status Public on May 19, 2020
Title Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Ph+ acute lymphoblastic leukemia (ALL) is characterized by the expression of an oncogenic fusion kinase termed BCR-ABL1. Here, we show that interleukin 7 receptor (IL7R) interacts with the chemokine receptor CXCR4 to recruit BCR-ABL1 and JAK kinases in close proximity. Treatment with BCR-ABL1 kinase inhibitors result in elevated expression of IL7R which enable the survival of transformed cells when IL7 was added together with the kinase inhibitors. Importantly, treatment with anti-IL7R antibodies prevents leukemia development in xenotransplantation models using patient-derived Ph+ ALL cells. Our results suggest that the association between IL7R and CXCR4 serves as molecular platform for BCR-ABL1 induced transformation and development of Ph+ ALL. Targeting this platform with anti-IL7R antibody eliminates Ph+ ALL cells including those with resistance to commonly used ABL1 kinase inhibitors. Thus, anti-IL7R antibodies may provide alternative treatment options for ALL in general and may suppress incurable drug-resistant leukemia forms.
 
Overall design 6 individually generated control WT pre-B cell lines and 6 BCR-ABL-transformed pre-B cell counterparts were analyzed.
 
Contributor(s) Abdelrasoul H, Vadakumchery A, Werner M, Lenk L, Khadour A, Young M, El Ayoubi O, Vogiatzi F, Krämer M, Schmid V, Chen Z, Yousafzai Y, Cario G, Schrappe M, Müschen M, Halsey C, Mulaw MA, Schewe DM, Hobeika E, Alsadeq A, Jumaa H
Citation(s) 32581241
Submission date May 18, 2020
Last update date Jun 29, 2020
Contact name Marc Young
E-mail(s) marc.young@uni-ulm.de
Organization name Universitätsklinikum Ulm
Department Institute für Immunologie
Lab Jumaa Lab
Street address Albert-Einstein-Allee 11
City Ulm
State/province Baden-Württemberg
ZIP/Postal code 89081
Country Germany
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM4558717 pMIG_plus_1A
GSM4558718 pMIG_plus_1B
GSM4558719 pMIG_plus_1C
Relations
BioProject PRJNA633578
SRA SRP262173

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Supplementary file Size Download File type/resource
GSE150784_meta.feature.level.counts.csv.gz 693.2 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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