Search: onr:"swepub:oai:lup.lub.lu.se:3661c149-bc79-4dee-8088-bbae401eedce" >
Glucocorticoid-resi...
-
Chougule, Rohit A.Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups
(author)
Glucocorticoid-resistant B cell acute lymphoblastic leukemia displays receptor tyrosine kinase activation
- Article/chapterEnglish2019
Publisher, publication year, extent ...
-
2019-04-04
-
Springer Science and Business Media LLC,2019
Numbers
-
LIBRIS-ID:oai:lup.lub.lu.se:3661c149-bc79-4dee-8088-bbae401eedce
-
https://lup.lub.lu.se/record/3661c149-bc79-4dee-8088-bbae401eedceURI
-
https://doi.org/10.1038/s41525-019-0082-yDOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:art swepub-publicationtype
-
Subject category:ref swepub-contenttype
Notes
-
The response of childhood acute lymphoblastic leukemia (ALL) to dexamethasone predicts the long-term remission outcome. To explore the mechanisms of dexamethasone resistance in B cell ALL (B-ALL), we generated dexamethasone-resistant clones by prolonged treatment with dexamethasone. Using RNA-sequencing and high-throughput screening, we found that dexamethasone-resistant cells are dependent on receptor tyrosine kinases. Further analysis with phosphokinase arrays showed that the type III receptor tyrosine kinase FLT3 is constitutively active in resistant cells. Targeted next-generation and Sanger sequencing identified an internal tandem duplication mutation and a point mutation (R845G) in FLT3 in dexamethasone-resistant cells, which were not present in the corresponding sensitive clones. Finally, we showed that resistant cells displayed sensitivity to second-generation FLT3 inhibitors both in vitro and in vivo. Collectively, our data suggest that long-term dexamethasone treatment selects cells with a distinct genetic background, in this case oncogenic FLT3, and therefore therapies targeting FLT3 might be useful for the treatment of relapsed B-ALL patients.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Shah, KinjalLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)ki2651sh
(author)
-
Moharram, Sausan A.Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups(Swepub:lu)med-sm8
(author)
-
Vallon-Christersson, JohanLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-jvc
(author)
-
Kazi, Julhash U.Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-kui
(author)
-
Molekylär cancerforskningForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
-
In:npj Genomic Medicine: Springer Science and Business Media LLC4:12056-7944
Internet link
Find in a library
To the university's database