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Glucocorticoid-resi...
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Chougule, Rohit A.Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups
(författare)
Glucocorticoid-resistant B cell acute lymphoblastic leukemia displays receptor tyrosine kinase activation
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2019-04-04
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Springer Science and Business Media LLC,2019
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:3661c149-bc79-4dee-8088-bbae401eedce
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https://lup.lub.lu.se/record/3661c149-bc79-4dee-8088-bbae401eedceURI
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https://doi.org/10.1038/s41525-019-0082-yDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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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
(författare)
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Moharram, Sausan A.Lund University,Lunds universitet,Molekylär cancerforskning,Forskargrupper vid Lunds universitet,Molecular Cancer Research,Lund University Research Groups(Swepub:lu)med-sm8
(författare)
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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
(författare)
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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
(författare)
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Molekylär cancerforskningForskargrupper vid Lunds universitet
(creator_code:org_t)
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Ingår i:npj Genomic Medicine: Springer Science and Business Media LLC4:12056-7944
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