Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells

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Ullmark, ToveLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine (author)

Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells

Article/chapterEnglish2017

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Elsevier BV,2017
6 s.
electronicrdacarrier

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LIBRIS-ID:oai:lup.lub.lu.se:d2a7c9e4-26cc-448b-9ef5-52db9958af39
https://lup.lub.lu.se/record/d2a7c9e4-26cc-448b-9ef5-52db9958af39URI
https://doi.org/10.1016/j.bbrc.2016.11.114DOI

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Language:English
Summary in:English

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Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of . WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to . WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the . de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between . WT1 and . QPRT, we overexpressed . WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of . QPRT expression. WT1 knock-down gave a corresponding decrease in . QPRT gene and protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a conserved site in the first intron of the . QPRT gene. Upon overexpression in leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug imatinib, indicating possible anti-apoptotic functions, consistent with previous reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression was not correlated to increased NAD + levels, suggesting NAD + independent mechanisms. We conclude that . QPRT, encoding a protein with anti-apoptotic properties, is a novel and direct target gene of WT1 in leukemic cells.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Hematologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Hematology hsv//eng
Acute myeloid leukemia
NAD+
Promoter
QPRT
Transcription
WT1

Added entries (persons, corporate bodies, meetings, titles ...)

Montano, GiorgiaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-ggm (author)
Järvstråt, LinneaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-ljt (author)
Jernmark Nilsson, HelenaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-hje (author)
Håkansson, ErikLund University (author)
Drott, KristinaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)efor-kch (author)
Nilsson, BjörnLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)klin-bni (author)
Vidovic, KarinaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)efor-kvi (author)
Gullberg, UrbanLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)efor-ugu (author)
Avdelningen för hematologi och transfusionsmedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

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In:Biochemical and Biophysical Research Communications: Elsevier BV482:4, s. 802-8070006-291X

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By the author/editor: Ullmark, Tove; Montano, Giorgia; Järvstråt, Linne ...; Jernmark Nilsson ...; Håkansson, Erik; Drott, Kristina; show more...; Nilsson, Björn; Vidovic, Karina; Gullberg, Urban; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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