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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03722naa a2200529 4500 | |
| 001 | oai:DiVA.org:uu-310826 | |
| 003 | SwePub | |
| 008 | 161220s2017 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:135217503 | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3108262 URI |
| 024 | 7 | a https://doi.org/10.1038/leu.2016.2222 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1352175032 URI |
| 040 | a (SwePub)uud (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Kontro, M4 aut |
| 245 | 1 0 | a HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia |
| 264 | c 2016-08-08 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2017 |
| 338 | a print2 rdacarrier | |
| 520 | a Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to β2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.Leukemia advance online publication, 2 September 2016; doi:10.1038/leu.2016.222. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Hematologi0 (SwePub)302022 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Hematology0 (SwePub)302022 hsv//eng |
| 700 | 1 | a Kumar, A4 aut |
| 700 | 1 | a Majumder, M M4 aut |
| 700 | 1 | a Eldfors, S4 aut |
| 700 | 1 | a Parsons, A4 aut |
| 700 | 1 | a Pemovska, T4 aut |
| 700 | 1 | a Saarela, J4 aut |
| 700 | 1 | a Yadav, B4 aut |
| 700 | 1 | a Malani, D4 aut |
| 700 | 1 | a Fløisand, Y4 aut |
| 700 | 1 | a Höglund, Martinu Uppsala universitet,Hematologi4 aut0 (Swepub:uu)martinhl |
| 700 | 1 | a Remes, K4 aut |
| 700 | 1 | a Gjertsen, B T4 aut |
| 700 | 1 | a Kallioniemi, Ou Karolinska Institutet4 aut |
| 700 | 1 | a Wennerberg, K4 aut |
| 700 | 1 | a Heckman, C A4 aut |
| 700 | 1 | a Porkka, K4 aut |
| 710 | 2 | a Uppsala universitetb Hematologi4 org |
| 773 | 0 | t Leukemiad : Springer Science and Business Media LLCg 31:2, s. 301-309q 31:2<301-309x 0887-6924x 1476-5551 |
| 856 | 4 | u https://helda.helsinki.fi/bitstream/10138/178840/1/HOX_gene_expression_predicts_response.pdf |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-310826 |
| 856 | 4 8 | u https://doi.org/10.1038/leu.2016.222 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:135217503 |
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