WFRF:(Baumann Tycho)
Sökning: WFRF:(Baumann Tycho) > Transposon Mutagene...
- 4 av 4
- Föregående post
- Nästa post
- Till träfflistan
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia
-
- Pandzic, Tatjana (författare)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
-
- Larsson, Jimmy (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi
-
- He, Liqun (författare)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
- visa fler...
- visa färre...
- (creator_code:org_t)
- 2016
- 2016
- Engelska.
- Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 22:24, s. 6217-6227
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Purpose: To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Experimental Design: We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: In total, this screen identified 782 genes with transposon integrations in fludarabine-resistant pools of cells. One of the identified genes is a known resistance mediator DCK (deoxycytidine kinase), which encodes an enzyme that is essential for the phosphorylation of the prodrug to the active metabolite. BMP2K, a gene not previously linked to CLL, was also identified as a modulator of response to fludarabine. In addition, 10 of 782 transposon-targeted genes had previously been implicated in treatment resistance based on somatic mutations seen in patients refractory to fludarabine-based therapy. Functional characterization of these genes supported a significant role for ARID5B and BRAF in fludarabine sensitivity. Finally, pathway analysis of transposon-targeted genes and RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Conclusions: To our knowledge, this is the first forward genetic screen for chemotherapy resistance in CLL. The screen pinpointed novel genes and pathways involved in fludarabine resistance along with previously known resistance mechanisms. Transposon screens can therefore aid interpretation of cancer genome sequencing data in the identification of genes modifying sensitivity to chemotherapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
- Clinical Cancer Research (Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- 4 av 4
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Pandzic, Tatjana
- Larsson, Jimmy
- He, Liqun
- Kundu, Snehangsh ...
- Ban, Kenneth
- Ali, Muhammad Ak ...
- visa fler...
- Hellström, Ander ...
- Schuh, Anna
- Clifford, Ruth
- Blakemore, Stuar ...
- Strefford, Jonat ...
- Baumann, Tycho
- Lopez-Guillermo, ...
- Campo, Elias
- Ljungström, Vikt ...
- Mansouri, Larry
- Rosenquist, Rich ...
- Sjöblom, Tobias
- Hellström, Mats
- visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Klinisk medicin
- och Cancer och onkol ...
- Artiklar i publikationen
- Clinical Cancer ...
- Av lärosätet
- Uppsala universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
