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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
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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.
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Overall design |
6 individually generated control WT pre-B cell lines and 6 BCR-ABL-transformed pre-B cell counterparts were analyzed.
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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 |
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Submission date |
May 18, 2020 |
Last update date |
Jun 29, 2020 |
Contact name |
Marc Young |
E-mail(s) |
marc.young@uni-ulm.de
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Organization name |
Universitätsklinikum Ulm
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Department |
Institute für Immunologie
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Lab |
Jumaa Lab
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Street address |
Albert-Einstein-Allee 11
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City |
Ulm |
State/province |
Baden-Württemberg |
ZIP/Postal code |
89081 |
Country |
Germany |
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Platforms (1) |
GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA633578 |
SRA |
SRP262173 |
Supplementary file |
Size |
Download |
File type/resource |
GSE150784_meta.feature.level.counts.csv.gz |
693.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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