Sökning: onr:"swepub:oai:lup.lub.lu.se:3661c149-bc79-4dee-8088-bbae401eedce" >
Glucocorticoid-resi...
Glucocorticoid-resistant B cell acute lymphoblastic leukemia displays receptor tyrosine kinase activation
-
- Chougule, Rohit A. (författare)
- Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups
-
- Shah, Kinjal (författare)
- 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
-
- Moharram, Sausan A. (författare)
- Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups
-
visa fler...
-
- Vallon-Christersson, Johan (författare)
- Lund 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
-
- Kazi, Julhash U. (författare)
- 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
-
visa färre...
-
(creator_code:org_t)
- 2019-04-04
- 2019
- Engelska.
-
Ingår i: npj Genomic Medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4:1
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://www.nature.c...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas