دورية أكاديمية
IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.
| العنوان: | IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia. |
|---|---|
| المؤلفون: | Aubrey BJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Cutler JA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Bourgeois W; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA., Donovan KA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA., Gu S; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Hatton C; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Perlee S; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Perner F; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Internal Medicine C, Universitaetsmedizin Greifswald, Greifswald, Germany., Rahnamoun H; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Theall ACP; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Henrich JA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Zhu Q; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA., Nowak RP; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA., Kim YJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Parvin S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Cremer A; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Hematology-Oncology, University Hospital Frankfurt, Frankfurt/Main, Germany.; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany., Olsen SN; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Eleuteri NA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA., Pikman Y; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA., McGeehan GM; Syndax Pharmaceuticals, Waltham, MA, USA., Stegmaier K; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA.; The Broad Institute of MIT and Harvard, Cambridge, MA, USA., Letai A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Fischer ES; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA., Liu XS; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Armstrong SA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. scott_armstrong@dfci.harvard.edu.; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA. scott_armstrong@dfci.harvard.edu. |
| المصدر: | Nature cancer [Nat Cancer] 2022 May; Vol. 3 (5), pp. 595-613. Date of Electronic Publication: 2022 May 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101761119 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-1347 (Electronic) Linking ISSN: 26621347 NLM ISO Abbreviation: Nat Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Publishing Group, [2020]- |
| مواضيع طبية MeSH: | Leukemia, Myeloid, Acute*/drug therapy, Chromatin ; Gene Expression ; Humans ; Ikaros Transcription Factor/metabolism ; Myeloid Ecotropic Viral Integration Site 1 Protein/genetics ; Transcription Factors/genetics |
| مستخلص: | Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation. Furthermore, IKAROS displays an unexpected functional cooperativity and extensive chromatin co-occupancy with mixed lineage leukemia (MLL)1-MENIN and the regulator MEIS1 and an extensive hematopoietic transcriptional complex involving homeobox (HOX)A10, MEIS1 and IKAROS. This dependency could be therapeutically exploited by inducing IKAROS protein degradation with immunomodulatory imide drugs (IMiDs). Finally, we demonstrate that combined IKAROS degradation and MENIN inhibition effectively disrupts leukemogenic transcriptional networks, resulting in synergistic killing of leukemia cells and providing a paradigm for improved drug targeting of transcription and an opportunity for rapid clinical translation. (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| التعليقات: | Comment in: Nat Cancer. 2022 May;3(5):528-529. (PMID: 35624338) |
| References: | Valk, P. J. et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N. Engl. J. Med. 350, 1617–1628 (2004). (PMID: 1508469410.1056/NEJMoa040465) Bullinger, L. et al. Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N. Engl. J. Med. 350, 1605–1616 (2004). (PMID: 1508469310.1056/NEJMoa031046) Krivtsov, A. V., Hoshii, T. & Armstrong, S. A. Mixed-lineage leukemia fusions and chromatin in leukemia. Cold Spring Harb. Perspect. Med. 7, a026658 (2017). Novershtern, N. et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 144, 296–309 (2011). (PMID: 21241896304986410.1016/j.cell.2011.01.004) Yokoyama, A. et al. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell 123, 207–218 (2005). (PMID: 1623914010.1016/j.cell.2005.09.025) Yokoyama, A. & Cleary, M. L. Menin critically links MLL proteins with LEDGF on cancer-associated target genes. Cancer Cell 14, 36–46 (2008). (PMID: 18598942269259110.1016/j.ccr.2008.05.003) Okada, Y. et al. hDOT1L links histone methylation to leukemogenesis. Cell 121, 167–178 (2005). (PMID: 1585102510.1016/j.cell.2005.02.020) Bernt, K. M. et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 20, 66–78 (2011). (PMID: 21741597332980310.1016/j.ccr.2011.06.010) Smith, E., Lin, C. & Shilatifard, A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 25, 661–672 (2011). (PMID: 21460034307092910.1101/gad.2015411) Brown, F. C. et al. MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia. Cancer Discov. 8, 478–497 (2018). (PMID: 29431698588257110.1158/2159-8290.CD-17-1271) Krivtsov, A. V. et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442, 818–822 (2006). (PMID: 1686211810.1038/nature04980) Placke, T. et al. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood 124, 13–23 (2014). (PMID: 24764564419061710.1182/blood-2014-02-558114) Faber, J. et al. HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood 113, 2375–2385 (2009). (PMID: 19056693265626710.1182/blood-2007-09-113597) Guo, H. et al. PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia. Int. J. Cancer 141, 324–335 (2017). (PMID: 2841138110.1002/ijc.30739) Kumar, A. R. et al. A role for MEIS1 in MLL-fusion gene leukemia. Blood 113, 1756–1758 (2009). (PMID: 19109563264766510.1182/blood-2008-06-163287) Collins, C. et al. C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc. Natl Acad. Sci. USA 111, 9899–9904 (2014). (PMID: 24958854410335010.1073/pnas.1402238111) Wilkinson, A. C. et al. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Rep. 3, 116–127 (2013). (PMID: 23352661360723210.1016/j.celrep.2012.12.016) Sun, Y. et al. HOXA9 reprograms the enhancer landscape to promote leukemogenesis. Cancer Cell 34, 643–658 (2018). (PMID: 30270123617944910.1016/j.ccell.2018.08.018) Cusan, M. et al. LSD1 inhibition exerts its antileukemic effect by recommissioning PU.1- and C/EBPα-dependent enhancers in AML. Blood 131, 1730–1742 (2018). (PMID: 29453291589786810.1182/blood-2017-09-807024) Zhu, N. et al. MLL-AF9- and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C. J. Clin. Invest. 126, 997–1011 (2016). (PMID: 26878175476734710.1172/JCI82978) Zeisig, B. B. et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol. Cell. Biol. 24, 617–628 (2004). (PMID: 1470173534379610.1128/MCB.24.2.617-628.2004) Kuhn, M. W. et al. Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov. 6, 1166–1181 (2016). (PMID: 27535106558480810.1158/2159-8290.CD-16-0237) Bradner, J. E., Hnisz, D. & Young, R. A. Transcriptional addiction in cancer. Cell 168, 629–643 (2017). (PMID: 28187285530855910.1016/j.cell.2016.12.013) Krivtsov, A. V. et al. A menin–MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia. Cancer Cell 36, 660–673 (2019). (PMID: 31821784722711710.1016/j.ccell.2019.11.001) Borkin, D. et al. Pharmacologic inhibition of the menin–MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 27, 589–602 (2015). (PMID: 25817203441585210.1016/j.ccell.2015.02.016) Klossowski, S. et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J. Clin. Invest. 130, 981–997 (2020). (PMID: 31855575699415410.1172/JCI129126) Daigle, S. R. et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 122, 1017–1025 (2013). (PMID: 23801631373902910.1182/blood-2013-04-497644) Perner, F. et al. Novel inhibitors of the histone methyltransferase DOT1L show potent antileukemic activity in patient-derived xenografts. Blood 136, 1983–1988 (2020). (PMID: 32575123820956310.1182/blood.2020006113) Uckelmann, H. J. et al. Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia. Science 367, 586–590 (2020). (PMID: 32001657775479110.1126/science.aax5863) Stein, E. M. et al. The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. Blood 131, 2661–2669 (2018). (PMID: 29724899626565410.1182/blood-2017-12-818948) Perner, F. & Armstrong, S. A. Targeting chromatin complexes in myeloid malignancies and beyond: from basic mechanisms to clinical innovation. Cells 9, 2721 (2020). Wang, B. et al. Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute. Nat. Protoc. 14, 756–780 (2019). (PMID: 30710114686272110.1038/s41596-018-0113-7) Lai, A. Y. & Wade, P. A. Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat. Rev. Cancer 11, 588–596 (2011). (PMID: 21734722415752410.1038/nrc3091) Cerami, E. et al. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012). (PMID: 2258887710.1158/2159-8290.CD-12-0095) Meyers, R. M. et al. Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells. Nat. Genet. 49, 1779–1784 (2017). (PMID: 29083409570919310.1038/ng.3984) Brunetti, L. et al. Mutant NPM1 maintains the leukemic state through HOX expression. Cancer Cell 34, 499–512 (2018). (PMID: 30205049615991110.1016/j.ccell.2018.08.005) Kronke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301–305 (2014). (PMID: 2429262510.1126/science.1244851) Lu, G. et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343, 305–309 (2014). (PMID: 2429262310.1126/science.1244917) Kronke, J. et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523, 183–188 (2015). (PMID: 26131937485391010.1038/nature14610) Donovan, K. A. et al. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. eLife 7, e38430 (2018). Guenther, M. G. et al. Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia. Genes Dev. 22, 3403–3408 (2008). (PMID: 19141473260707310.1101/gad.1741408) Skene, P. J. & Henikoff, S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. eLife 6, e21856 (2017). Meers, M. P., Bryson, T. D., Henikoff, J. G. & Henikoff, S. Improved CUT&RUN chromatin profiling tools. eLife 8, e46314 (2019). Zhu, Q., Liu, N., Orkin, S. H. & Yuan, G. C. CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis. Genome Biol. 20, 192 (2019). (PMID: 31500663673424910.1186/s13059-019-1802-4) Fulco, C. P. et al. Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations. Nat. Genet. 51, 1664–1669 (2019). (PMID: 31784727688658510.1038/s41588-019-0538-0) Ryan, J. A., Brunelle, J. K. & Letai, A. Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4 + CD8 + thymocytes. Proc. Natl Acad. Sci. USA 107, 12895–12900 (2010). (PMID: 20615979291990010.1073/pnas.0914878107) Samavarchi-Tehrani, P., Samson, R. & Gingras, A. C. Proximity dependent biotinylation: key enzymes and adaptation to proteomics approaches. Mol. Cell. Proteomics 19, 757–773 (2020). (PMID: 32127388719657910.1074/mcp.R120.001941) Guirguis, A. A. & Ebert, B. L. Lenalidomide: deciphering mechanisms of action in myeloma, myelodysplastic syndrome and beyond. Curr. Opin. Cell Biol. 37, 61–67 (2015). (PMID: 2651245410.1016/j.ceb.2015.10.004) Fink, E. C. et al. Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice. Blood 132, 1535–1544 (2018). (PMID: 30064974617256310.1182/blood-2018-05-852798) Francis, O. L., Payne, J. L., Su, R. J. & Payne, K. J. Regulator of myeloid differentiation and function: the secret life of Ikaros. World J. Biol. Chem. 2, 119–125 (2011). (PMID: 21765977313585810.4331/wjbc.v2.i6.119) Boutboul, D. et al. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. J. Clin. Invest. 128, 3071–3087 (2018). (PMID: 29889099602600010.1172/JCI98164) Yoshida, T., Ng, S. Y., Zuniga-Pflucker, J. C. & Georgopoulos, K. Early hematopoietic lineage restrictions directed by Ikaros. Nat. Immunol. 7, 382–391 (2006). (PMID: 1651839310.1038/ni1314) Martinez-Hoyer, S. et al. Loss of lenalidomide-induced megakaryocytic differentiation leads to therapy resistance in del(5q) myelodysplastic syndrome. Nat. Cell Biol. 22, 526–533 (2020). (PMID: 3225139810.1038/s41556-020-0497-9) Georgopoulos, K. Haematopoietic cell-fate decisions, chromatin regulation and ikaros. Nat. Rev. Immunol. 2, 162–174 (2002). (PMID: 1191306710.1038/nri747) Bottardi, S., Mavoungou, L. & Milot, E. IKAROS: a multifunctional regulator of the polymerase II transcription cycle. Trends Genet. 31, 500–508 (2015). (PMID: 2604962710.1016/j.tig.2015.05.003) Ding, Y. et al. Ikaros tumor suppressor function includes induction of active enhancers and super-enhancers along with pioneering activity. Leukemia 33, 2720–2731 (2019). (PMID: 31073152684207510.1038/s41375-019-0474-0) Scacheri, P. C. et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2, e51 (2006). (PMID: 16604156142878810.1371/journal.pgen.0020051) Skucha, A. et al. MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. Nat. Commun. 9, 1983 (2018). (PMID: 29777171595986610.1038/s41467-018-04329-y) Hughes, C. M. et al. Menin associates with a trithorax family histone methyltransferase complex and with the Hoxc8 locus. Mol. Cell 13, 587–597 (2004). (PMID: 1499272710.1016/S1097-2765(04)00081-4) Bres, V., Yoshida, T., Pickle, L. & Jones, K. A. SKIP interacts with c-Myc and menin to promote HIV-1 Tat transactivation. Mol. Cell 36, 75–87 (2009). (PMID: 19818711276628110.1016/j.molcel.2009.08.015) Agarwal, S. K. et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 96, 143–152 (1999). (PMID: 998950510.1016/S0092-8674(00)80967-8) Huang, J. et al. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 482, 542–546 (2012). (PMID: 22327296398379210.1038/nature10806) Wu, Y. et al. Disruption of the menin–MLL interaction triggers menin protein degradation via ubiquitin-proteasome pathway. Am. J. Cancer Res. 9, 1682–1694 (2019). (PMID: 314973506726985) Xie, C. H. et al. Efficacy and safety of lenalidomide for the treatment of acute myeloid leukemia: a systematic review and meta-analysis. Cancer Manag. Res. 10, 3637–3648 (2018). (PMID: 30271212615260310.2147/CMAR.S168610) Ebert, B. L. & Kronke, J. Inhibition of casein kinase 1 α in acute myeloid leukemia. N. Engl. J. Med. 379, 1873–1874 (2018). (PMID: 3040394510.1056/NEJMcibr1811318) Le Roy, A. et al. Immunomodulatory drugs exert anti-leukemia effects in acute myeloid leukemia by direct and immunostimulatory activities. Front. Immunol. 9, 977 (2018). (PMID: 29780393594582410.3389/fimmu.2018.00977) Fang, J. et al. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat. Med. 22, 727–734 (2016). (PMID: 27294874550758910.1038/nm.4127) Kluk, M. J. et al. Validation and implementation of a custom next-generation sequencing clinical assay for hematologic malignancies. J. Mol. Diagn. 18, 507–515 (2016). (PMID: 27339098570718610.1016/j.jmoldx.2016.02.003) Townsend, E. C. et al. The public repository of xenografts enables discovery and randomized phase II-like trials in mice. Cancer Cell 29, 574–586 (2016). (PMID: 27070704517799110.1016/j.ccell.2016.03.008) Chi, H. T. et al. Detection of exon 12 type A mutation of NPM1 gene in IMS-M2 cell line. Leuk. Res. 34, 261–262 (2010). (PMID: 1985450810.1016/j.leukres.2009.09.019) Fei, T. et al. Deciphering essential cistromes using genome-wide CRISPR screens. Proc. Natl Acad. Sci. USA 116, 25186–25195 (2019). (PMID: 31727847691117510.1073/pnas.1908155116) Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014). (PMID: 25476604429082410.1186/s13059-014-0554-4) Doench, J. G. et al. Rational design of highly active sgRNAs for CRISPR–Cas9-mediated gene inactivation. Nat. Biotechnol. 32, 1262–1267 (2014). (PMID: 25184501426273810.1038/nbt.3026) Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11, 1475–1489 (1983). (PMID: 682838632580910.1093/nar/11.5.1475) Lu, X. et al. MTA2/NuRD regulates B cell development and cooperates with OCA-B in controlling the pre-B to immature B cell transition. Cell Rep. 28, 472–485 (2019). (PMID: 31291582669061310.1016/j.celrep.2019.06.029) McAlister, G. C. et al. MultiNotch MS 3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal. Chem. 86, 7150–7158 (2014). (PMID: 24927332421586610.1021/ac502040v) R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2014). Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47–e47 (2015). (PMID: 25605792440251010.1093/nar/gkv007) Mellacheruvu, D. et al. The CRAPome: a contaminant repository for affinity purification–mass spectrometry data. Nat. Methods 10, 730–736 (2013). (PMID: 23921808377350010.1038/nmeth.2557) Olsen, S. N. et al. MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape. Mol. Cell 82, 1140–1155 (2022). (PMID: 3524543510.1016/j.molcel.2022.02.013) Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005). (PMID: 16199517123989610.1073/pnas.0506580102) Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003). (PMID: 1280845710.1038/ng1180) Iniguez, A. B. et al. Resistance to epigenetic-targeted therapy engenders tumor cell vulnerabilities associated with enhancer remodeling. Cancer Cell 34, 922–938 (2018). (PMID: 30537514635290910.1016/j.ccell.2018.11.005) Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). (PMID: 2310488610.1093/bioinformatics/bts635) Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009). (PMID: 19505943272300210.1093/bioinformatics/btp352) Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011). (PMID: 21221095334618210.1038/nbt.1754) Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015). (PMID: 2526070010.1093/bioinformatics/btu638) Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014). (PMID: 25516281430204910.1186/s13059-014-0550-8) Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012). (PMID: 22388286332238110.1038/nmeth.1923) Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016). (PMID: 2720794310.1093/bioinformatics/btw313) Tange, O. GNU parallel—the command-line power tool. The USENIX Magazine 36, 42–47 (2011). Gao, J. et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, pl1 (2013). (PMID: 23550210416030710.1126/scisignal.2004088) Wang, X. Q. D. et al. Three-dimensional regulation of HOXA cluster genes by a cis-element in hematopoietic stem cell and leukemia. Preprint at bioRxiv https://doi.org/10.1101/2020.04.16.017533 (2020). |
| معلومات مُعتمدة: | R35 CA242427 United States CA NCI NIH HHS; U54 CA231637 United States CA NCI NIH HHS; T32 HL007574 United States HL NHLBI NIH HHS; P50 CA206963 United States CA NCI NIH HHS; F32 CA250240 United States CA NCI NIH HHS; R01 CA176745 United States CA NCI NIH HHS; R01 CA214608 United States CA NCI NIH HHS; K08 CA222684 United States CA NCI NIH HHS; R01 CA204639 United States CA NCI NIH HHS; P01 CA066996 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Chromatin) 0 (Myeloid Ecotropic Viral Integration Site 1 Protein) 0 (Transcription Factors) 148971-36-2 (Ikaros Transcription Factor) |
| تواريخ الأحداث: | Date Created: 20220509 Date Completed: 20220530 Latest Revision: 20230519 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9404532 |
| DOI: | 10.1038/s43018-022-00366-1 |
| PMID: | 35534777 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. | تدمد: | 2662-1347 |
|---|---|
| DOI: | 10.1038/s43018-022-00366-1 |