PUBLICATION
High cystic fibrosis transmembrane conductance regulator expression in childhood B-cell acute lymphoblastic leukemia acts as a potential therapeutic target
- Authors
- Liu, M., Lin, Z., Wang, Y., Zhang, J., Zhou, M., Tsang, K.S., Liao, H., Chen, Y., Liu, Y., Zhang, X., Chan, H.C., Sun, H.
- ID
- ZDB-PUB-220412-12
- Date
- 2022
- Source
- Translational cancer research 11: 436-443 (Journal)
- Registered Authors
- Chan, Hsiao Chang, Sun, Huaqin
- Keywords
- CFTRinh-172, Cystic fibrosis transmembrane conductance regulator (CFTR), human B-cell acute lymphoblastic leukemia (human B-ALL), treatment
- MeSH Terms
- none
- PubMed
- 35402186 Full text @ Transl Cancer Res
Citation
Liu, M., Lin, Z., Wang, Y., Zhang, J., Zhou, M., Tsang, K.S., Liao, H., Chen, Y., Liu, Y., Zhang, X., Chan, H.C., Sun, H. (2022) High cystic fibrosis transmembrane conductance regulator expression in childhood B-cell acute lymphoblastic leukemia acts as a potential therapeutic target. Translational cancer research. 11:436-443.
Abstract
Background The role of cystic fibrosis transmembrane conductance regulator (CFTR) in hematopoiesis and adult leukemia has been demonstrated using a zebrafish model and leukemia cell lines in our previous works. Here, we continue to explore the association between CFTR and human childhood B-cell acute lymphoblastic leukemia (B-ALL).
Methods We continued to collect the peripheral blood and bone marrows of human childhood patients diagnosed with primary B-ALL as well as non-leukemia controls and isolated lymphocytes for analysis using western blotting and quantitative real-time polymerase chain reaction (qPCR) assay. Then, we used immunofluorescence, co-immunoprecipitation, western blotting, luciferase, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays to identify the interaction of CFTR with Wnt signaling in B-ALL. Finally, we established B-ALL xenograft model in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice using SUP-B15 cells, and examined whether the CFTR inhibitor CFTR-inh172 could active against SUP-B15-Dependent B-ALL in vivo.
Results Highly expressed CFTR protein and mRNA are associated with primary childhood B-ALL patients. Aberrantly upregulated CFTR and Wnt signaling, our previously reported CFTR-Dvl2-β-catenin pathway, is found in human childhood B-ALL patients. Interference with CFTR in B-ALL cell lines induces the downregulation of DVL2/β-catenin and Wnt downstream target accompanied by a reduction of cell proliferation. Furthermore, B-ALL cell lines SUP-B15 cell-transplanted NOD/SCID mice treated with CFTR inhibitor CFTRinh-172 had significantly longer survival and slower leukemia progression compared with mice treated with vehicle dimethyl sulfoxide (DMSO).
Conclusions These findings demonstrate that highly expressed CFTR is associated with human childhood B-ALL and the potential of CFTR inhibitor CFTR-inh172 for the treatment of human B-ALL.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping