Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes

[en] Acute myeloid leukemia (AML) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Using an original proteogenomic approach, we analyzed the major histocompatibility complex class I (MHC class I)-associated immunopeptidome of 19 primary AML samples and identified 58 tumor-specific antigens (TSAs). These TSAs bore no mutations and derived mainly (86%) from supposedly non-coding genomic regions. Two AML-specific aberrations were instrumental in the biogenesis of TSAs, intron retention, and epigenetic changes. Indeed, 48% of TSAs resulted from intron retention and translation, and their RNA expression correlated with mutations of epigenetic modifiers (e.g., DNMT3A). AML TSA-coding transcripts were highly shared among patients and were expressed in both blasts and leukemic stem cells. In AML patients, the predicted number of TSAs correlated with spontaneous expansion of cognate T cell receptor clonotypes, accumulation of activated cytotoxic T cells, immunoediting, and improved survival. These TSAs represent attractive targets for AML immunotherapy.

Disciplines :

Immunology & infectious disease

Author, co-author :

Ehx, Grégory ; Université de Liège - ULiège > GIGA I3 - Hematology

Larouche, Jean-David

Durette, Chantal

Laverdure, Jean-Philippe

Hesnard, Leslie

Vincent, Krystel

Hardy, Marie-Pierre

Thériault, Catherine

Rulleau, Caroline

Lanoix, Joël

More authors (12 more)

Language :

English

Title :

Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes

Publication date :

13 April 2021

Journal title :

Immunity

ISSN :

1074-7613

eISSN :

1097-4180

Publisher :

Cell Press, United States - Massachusetts

Volume :

Issue :

Pages :

737-752

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.cell.com/immunity/fulltext/S1074-7613(21)00087-X

Available on ORBi :

since 06 May 2021

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Bibliography

Adamopoulou, E., Tenzer, S., Hillen, N., Klug, P., Rota, I.A., Tietz, S., Gebhardt, M., Stevanovic, S., Schild, H., Tolosa, E., et al. Exploring the MHC-peptide matrix of central tolerance in the human thymus. Nat. Commun., 4, 2013, 2039.
Andreatta, M., Nielsen, M., Gapped sequence alignment using artificial neural networks: application to the MHC class I system. Bioinformatics 32 (2016), 511–517.
Audemard, E.O., Gendron, P., Feghaly, A., Lavallée, V.P., Hébert, J., Sauvageau, G., Lemieux, S., Targeted variant detection using unaligned RNA-Seq reads. Life Sci. Alliance, 2, 2019, 2.
Audoux, J., Philippe, N., Chikhi, R., Salson, M., Gallopin, M., Gabriel, M., Le Coz, J., Drouineau, E., Commes, T., Gautheret, D., DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition. Genome Biol., 18, 2017, 243.
Avigan, D., Rosenblatt, J., Vaccine therapy in hematologic malignancies. Blood 131 (2018), 2640–2650.
Bamezai, S., Rawat, V.P., Buske, C., Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing. Stem Cells 30 (2012), 2603–2611.
Berlin, C., Kowalewski, D.J., Schuster, H., Mirza, N., Walz, S., Handel, M., Schmid-Horch, B., Salih, H.R., Kanz, L., Rammensee, H.G., et al. Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy. Leukemia 29 (2015), 647–659.
Boegel, S., Löwer, M., Bukur, T., Sorn, P., Castle, J.C., Sahin, U., HLA and proteasome expression body map. BMC Med. Genomics, 11, 2018, 36.
Bollard, C.M., Gottschalk, S., Leen, A.M., Weiss, H., Straathof, K.C., Carrum, G., Khalil, M., Wu, M.F., Huls, M.H., Chang, C.C., et al. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood 110 (2007), 2838–2845.
Bouwmeester, R., Gabriels, R., Hulstaert, N., Martens, L., Degroeve, S., DeepLC can predict retention times for peptides that carry as-yet unseen modifications. bioRxiv, 2020 2020.2003.2028.013003.
Bray, N.L., Pimentel, H., Melsted, P., Pachter, L., Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34 (2016), 525–527.
Chapuis, A.G., Egan, D.N., Bar, M., Schmitt, T.M., McAfee, M.S., Paulson, K.G., Voillet, V., Gottardo, R., Ragnarsson, G.B., Bleakley, M., et al. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat. Med. 25 (2019), 1064–1072.
Charni, S., de Bettignies, G., Rathore, M.G., Aguiló, J.I., van den Elsen, P.J., Haouzi, D., Hipskind, R.A., Enriquez, J.A., Sanchez-Beato, M., Pardo, J., et al. Oxidative phosphorylation induces de novo expression of the MHC class I in tumor cells through the ERK5 pathway. J. Immunol. 185 (2010), 3498–3503.
Chen, J., Brunner, A.D., Cogan, J.Z., Nuñez, J.K., Fields, A.P., Adamson, B., Itzhak, D.N., Li, J.Y., Mann, M., Leonetti, M.D., Weissman, J.S., Pervasive functional translation of noncanonical human open reading frames. Science 367 (2020), 1140–1146.
Chong, C., Müller, M., Pak, H., Harnett, D., Huber, F., Grun, D., Leleu, M., Auger, A., Arnaud, M., Stevenson, B.J., et al. Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes. Nat. Commun., 11, 2020, 1293.
Corces, M.R., Buenrostro, J.D., Wu, B., Greenside, P.G., Chan, S.M., Koenig, J.L., Snyder, M.P., Pritchard, J.K., Kundaje, A., Greenleaf, W.J., et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat. Genet. 48 (2016), 1193–1203.
Cosma, G.L., Eisenlohr, L.C., Impact of epitope density on CD8+ T cell development and function. Mol. Immunol. 113 (2019), 120–125.
Coulie, P.G., Van den Eynde, B.J., van der Bruggen, P., Boon, T., Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat. Rev. Cancer 14 (2014), 135–146.
Courcelles, M., Durette, C., Daouda, T., Laverdure, J.P., Vincent, K., Lemieux, S., Perreault, C., Thibault, P., MAPDP: A Cloud-Based Computational Platform for Immunopeptidomics Analyses. J. Proteome Res. 19 (2020), 1873–1881.
Danilova, L., Anagnostou, V., Caushi, J.X., Sidhom, J.W., Guo, H., Chan, H.Y., Suri, P., Tam, A., Zhang, J., Asmar, M.E., et al. The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity. Cancer Immunol. Res. 6 (2018), 888–899.
Daouda, T., Perreault, C., Lemieux, S., pyGeno: A Python package for precision medicine and proteogenomics. F1000Res., 5, 2016, 381.
de Sá Machado Araújo, G., da Silva Francisco Junior, R., Dos Santos Ferreira, C., Mozer Rodrigues, P.T., Terra Machado, D., Louvain de Souza, T., Teixeira de Souza, J., Figueiredo Osorio da Silva, C., Alves da Silva, A.F., Andrade, C.C.F., et al. Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues. Front. Genet., 9, 2018, 36.
Di Stasi, A., Jimenez, A.M., Minagawa, K., Al-Obaidi, M., Rezvani, K., Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies. Front. Immunol., 6, 2015, 36.
Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., Gingeras, T.R., STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 (2013), 15–21.
Dutoit, V., Rubio-Godoy, V., Pittet, M.J., Zippelius, A., Dietrich, P.Y., Legal, F.A., Guillaume, P., Romero, P., Cerottini, J.C., Houghten, R.A., et al. Degeneracy of antigen recognition as the molecular basis for the high frequency of naive A2/Melan-a peptide multimer(+) CD8(+) T cells in humans. J. Exp. Med. 196 (2002), 207–216.
Dvinge, H., Bradley, R.K., Widespread intron retention diversifies most cancer transcriptomes. Genome Med., 7, 2015, 45.
Efremova, M., Finotello, F., Rieder, D., Trajanoski, Z., Neoantigens Generated by Individual Mutations and Their Role in Cancer Immunity and Immunotherapy. Front. Immunol., 8, 2017, 1679.
Egen, J.G., Ouyang, W., Wu, L.C., Human Anti-tumor Immunity: Insights from Immunotherapy Clinical Trials. Immunity 52 (2020), 36–54.
Ehx, G., Perreault, C., Discovery and characterization of actionable tumor antigens. Genome Med., 11, 2019, 29.
Elias, J.E., Gygi, S.P., Target-decoy search strategy for mass spectrometry-based proteomics. Methods Mol. Biol. 604 (2010), 55–71.
Eng, J.K., Hoopmann, M.R., Jahan, T.A., Egertson, J.D., Noble, W.S., MacCoss, M.J., A deeper look into Comet–implementation and features. J. Am. Soc. Mass Spectrom. 26 (2015), 1865–1874.
Eppert, K., Takenaka, K., Lechman, E.R., Waldron, L., Nilsson, B., van Galen, P., Metzeler, K.H., Poeppl, A., Ling, V., Beyene, J., et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat. Med. 17 (2011), 1086–1093.
Fennell, K.A., Bell, C.C., Dawson, M.A., Epigenetic therapies in acute myeloid leukemia: where to from here?. Blood 134 (2019), 1891–1901.
Fergusson, J.R., Morgan, M.D., Bruchard, M., Huitema, L., Heesters, B.A., van Unen, V., van Hamburg, J.P., van der Wel, N.N., Picavet, D., Koning, F., et al. Maturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens. Front. Immunol., 9, 2019, 2902.
Figueroa, M.E., Abdel-Wahab, O., Lu, C., Ward, P.S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H.F., et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18 (2010), 553–567.
Figueroa, M.E., Lugthart, S., Li, Y., Erpelinck-Verschueren, C., Deng, X., Christos, P.J., Schifano, E., Booth, J., van Putten, W., Skrabanek, L., et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 17 (2010), 13–27.
Garrison, E., Marth, G., Haplotype-based variant detection from short-read sequencing. arXiv, 2012 Genomics.
Gaujoux, R., Seoighe, C., A flexible R package for nonnegative matrix factorization. BMC Bioinformatics, 11, 2010, 367.
Greiner, J., Hofmann, S., Schmitt, M., Götz, M., Wiesneth, M., Schrezenmeier, H., Bunjes, D., Döhner, H., Bullinger, L., Acute myeloid leukemia with mutated nucleophosmin 1: an immunogenic acute myeloid leukemia subtype and potential candidate for immune checkpoint inhibition. Haematologica 102 (2017), e499–e501.
Gu, M., Zwiebel, M., Ong, S.H., Boughton, N., Nomdedeu, J., Basheer, F., Nannya, Y., Quiros, P.M., Ogawa, S., Cazzola, M., et al. RNAmut: robust identification of somatic mutations in acute myeloid leukemia using RNA-sequencing. Haematologica 105 (2020), e290–e293.
Gutierrez, S.E., Romero-Oliva, F.A., Epigenetic changes: a common theme in acute myelogenous leukemogenesis. J. Hematol. Oncol., 6, 2013, 57.
Hardy, M.-P., Vincent, K., Perreault, C., The Genomic Landscape of Antigenic Targets for T Cell-Based Leukemia Immunotherapy. Front. Immunol., 10, 2019, 2934.
He, H., Kondo, Y., Ishiyama, K., Alatrash, G., Lu, S., Cox, K., Qiao, N., Clise-Dwyer, K., St John, L., Sukhumalchandra, P., et al. Two unique HLA-A∗0201 restricted peptides derived from cyclin E as immunotherapeutic targets in leukemia. Leukemia 34 (2020), 1626–1636.
Hesnard, L., Legoux, F., Gautreau, L., Moyon, M., Baron, O., Devilder, M.C., Bonneville, M., Saulquin, X., Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus. Eur. J. Immunol. 46 (2016), 560–569.
Janelle, V., Carli, C., Taillefer, J., Orio, J., Delisle, J.S., Defining novel parameters for the optimal priming and expansion of minor histocompatibility antigen-specific T cells in culture. J. Transl. Med., 13, 2015, 123.
Jung, N., Dai, B., Gentles, A.J., Majeti, R., Feinberg, A.P., An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis. Nat. Commun., 6, 2015, 8489.
Knaus, H.A., Berglund, S., Hackl, H., Blackford, A.L., Zeidner, J.F., Montiel-Esparza, R., Mukhopadhyay, R., Vanura, K., Blazar, B.R., Karp, J.E., et al. Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy. JCI Insight, 3, 2018, 3.
Krokhin, O.V., Sequence-specific retention calculator. Algorithm for peptide retention prediction in ion-pair RP-HPLC: application to 300- and 100-A pore size C18 sorbents. Anal. Chem. 78 (2006), 7785–7795.
Lagus, H., Klaas, M., Juteau, S., Elomaa, O., Kere, J., Vuola, J., Jaks, V., Kankuri, E., Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial - reflections on psoriatic inflammation. Sci. Rep., 9, 2019, 19136.
Lamoliatte, F., McManus, F.P., Maarifi, G., Chelbi-Alix, M.K., Thibault, P., Uncovering the SUMOylation and ubiquitylation crosstalk in human cells using sequential peptide immunopurification. Nat. Commun., 8, 2017, 14109.
Larouche, J.D., Trofimov, A., Hesnard, L., Ehx, G., Zhao, Q., Vincent, K., Durette, C., Gendron, P., Laverdure, J.P., Bonneil, É., et al. Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues. Genome Med., 12, 2020, 40.
Laumont, C.M., Daouda, T., Laverdure, J.P., Bonneil, É., Caron-Lizotte, O., Hardy, M.P., Granados, D.P., Durette, C., Lemieux, S., Thibault, P., Perreault, C., Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames. Nat. Commun., 7, 2016, 10238.
Laumont, C.M., Vincent, K., Hesnard, L., Audemard, É., Bonneil, É., Laverdure, J.P., Gendron, P., Courcelles, M., Hardy, M.P., Côté, C., et al. Noncoding regions are the main source of targetable tumor-specific antigens. Sci. Transl. Med., 10, 2018, 10.
Lavallée, V.P., Baccelli, I., Krosl, J., Wilhelm, B., Barabé, F., Gendron, P., Boucher, G., Lemieux, S., Marinier, A., Meloche, S., et al. The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias. Nat. Genet. 47 (2015), 1030–1037.
Lavallée, V.P., Krosl, J., Lemieux, S., Boucher, G., Gendron, P., Pabst, C., Boivin, I., Marinier, A., Guidos, C.J., Meloche, S., et al. Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors. Blood 127 (2016), 3054–3061.
Lavallée, V.P., Lemieux, S., Boucher, G., Gendron, P., Boivin, I., Armstrong, R.N., Sauvageau, G., Hébert, J., RNA-sequencing analysis of core binding factor AML identifies recurrent ZBTB7A mutations and defines RUNX1-CBFA2T3 fusion signature. Blood 127 (2016), 2498–2501.
Lawrence, M.S., Stojanov, P., Polak, P., Kryukov, G.V., Cibulskis, K., Sivachenko, A., Carter, S.L., Stewart, C., Mermel, C.H., Roberts, S.A., et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499 (2013), 214–218.
Legat, A., Maby-El Hajjami, H., Baumgaertner, P., Cagnon, L., Abed Maillard, S., Geldhof, C., Iancu, E.M., Lebon, L., Guillaume, P., Dojcinovic, D., et al. Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients–Report of a Phase I/IIa Clinical Trial. Clin. Cancer Res. 22 (2016), 1330–1340.
Lewinsky, H., Barak, A.F., Huber, V., Kramer, M.P., Radomir, L., Sever, L., Orr, I., Mirkin, V., Dezorella, N., Shapiro, M., et al. CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia. J. Clin. Invest. 128 (2018), 5465–5478.
Ley, T.J., Miller, C., Ding, L., Raphael, B.J., Mungall, A.J., Robertson, A., Hoadley, K., Triche, T.J. Jr., Laird, P.W., Baty, J.D., et al., Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368 (2013), 2059–2074.
Li, B., Li, T., Wang, B., Dou, R., Zhang, J., Liu, J.S., Liu, X.S., Ultrasensitive detection of TCR hypervariable-region sequences in solid-tissue RNA-seq data. Nat. Genet. 49 (2017), 482–483.
Li, H., A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 27 (2011), 2987–2993.
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
Li, S., Garrett-Bakelman, F.E., Chung, S.S., Sanders, M.A., Hricik, T., Rapaport, F., Patel, J., Dillon, R., Vijay, P., Brown, A.L., et al. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat. Med. 22 (2016), 792–799.
Liu, L., Xu, F., Chang, C.-K., He, Q., Wu, L.-Y., Zhang, Z., Li, X., MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-mediated epigenetic repression of p21. Cell Death Dis., 8, 2017, e3126.
Löffler, M.W., Mohr, C., Bichmann, L., Freudenmann, L.K., Walzer, M., Schroeder, C.M., Trautwein, N., Hilke, F.J., Zinser, R.S., Mühlenbruch, L., et al., HEPAVAC Consortium. Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma. Genome Med., 11, 2019, 28.
Logtenberg, M.E.W., Scheeren, F.A., Schumacher, T.N., The CD47-SIRPα Immune Checkpoint. Immunity 52 (2020), 742–752.
Luo, K., Yuan, J., Shan, Y., Li, J., Xu, M., Cui, Y., Tang, W., Wan, B., Zhang, N., Wu, Y., Yu, L., Activation of transcriptional activities of AP1 and SRE by a novel zinc finger protein ZNF445. Gene 367 (2006), 89–100.
Macrae, T., Sargeant, T., Lemieux, S., Hébert, J., Deneault, E., Sauvageau, G., RNA-Seq reveals spliceosome and proteasome genes as most consistent transcripts in human cancer cells. PLoS ONE, 8, 2013, e72884.
Maere, S., Heymans, K., Kuiper, M., BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21 (2005), 3448–3449.
Maiga, A., Lemieux, S., Pabst, C., Lavallée, V.P., Bouvier, M., Sauvageau, G., Hébert, J., Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets. Blood Cancer J., 6, 2016, e431.
Marçais, G., Kingsford, C., A fast, lock-free approach for efficient parallel counting of occurrences of k-mers. Bioinformatics 27 (2011), 764–770.
Maslak, P.G., Dao, T., Bernal, Y., Chanel, S.M., Zhang, R., Frattini, M., Rosenblat, T., Jurcic, J.G., Brentjens, R.J., Arcila, M.E., et al. Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv. 2 (2018), 224–234.
Merico, D., Isserlin, R., Stueker, O., Emili, A., Bader, G.D., Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE, 5, 2010, e13984.
Middleton, R., Gao, D., Thomas, A., Singh, B., Au, A., Wong, J.J., Bomane, A., Cosson, B., Eyras, E., Rasko, J.E., Ritchie, W., IRFinder: assessing the impact of intron retention on mammalian gene expression. Genome Biol., 18, 2017, 51.
Noronha, N., Ehx, G., Meunier, M.C., Laverdure, J.P., Thériault, C., Perreault, C., Major multilevel molecular divergence between THP-1 cells from different biorepositories. Int. J. Cancer 147 (2020), 2000–2006.
Ntziachristos, P., Abdel-Wahab, O., Aifantis, I., Emerging concepts of epigenetic dysregulation in hematological malignancies. Nat. Immunol. 17 (2016), 1016–1024.
Ogishi, M., Yotsuyanagi, H., Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space. Front. Immunol., 10, 2019, 827.
Pabst, C., Bergeron, A., Lavallée, V.P., Yeh, J., Gendron, P., Norddahl, G.L., Krosl, J., Boivin, I., Deneault, E., Simard, J., et al. GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo. Blood 127 (2016), 2018–2027.
Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V.I., Paschka, P., Roberts, N.D., Potter, N.E., Heuser, M., Thol, F., Bolli, N., et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N. Engl. J. Med. 374 (2016), 2209–2221.
Pearson, H., Daouda, T., Granados, D.P., Durette, C., Bonneil, E., Courcelles, M., Rodenbrock, A., Laverdure, J.P., Côté, C., Mader, S., et al. MHC class I-associated peptides derive from selective regions of the human genome. J. Clin. Invest. 126 (2016), 4690–4701.
Qazilbash, M.H., Wieder, E., Thall, P.F., Wang, X., Rios, R., Lu, S., Kanodia, S., Ruisaard, K.E., Giralt, S.A., Estey, E.H., et al. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31 (2017), 697–704.
Quinlan, A.R., Hall, I.M., BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26 (2010), 841–842.
Rashidi, A., Walter, R.B., Antigen-specific immunotherapy for acute myeloid leukemia: where are we now, and where do we go from here?. Expert Rev. Hematol. 9 (2016), 335–350.
Ritchie, M.E., Phipson, B., Wu, D., Hu, Y., Law, C.W., Shi, W., Smyth, G.K., limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 43, 2015, e47.
Robinson, J.T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E.S., Getz, G., Mesirov, J.P., Integrative genomics viewer. Nat. Biotechnol. 29 (2011), 24–26.
Robinson, M.D., McCarthy, D.J., Smyth, G.K., edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 (2010), 139–140.
Rogers, M.F., Shihab, H.A., Mort, M., Cooper, D.N., Gaunt, T.R., Campbell, C., FATHMM-XF: accurate prediction of pathogenic point mutations via extended features. Bioinformatics 34 (2018), 511–513.
Sarkizova, S., Klaeger, S., Le, P.M., Li, L.W., Oliveira, G., Keshishian, H., Hartigan, C.R., Zhang, W., Braun, D.A., Ligon, K.L., et al. A large peptidome dataset improves HLA class I epitope prediction across most of the human population. Nat. Biotechnol. 38 (2020), 199–209.
Schulz, W.A., Steinhoff, C., Florl, A.R., Methylation of endogenous human retroelements in health and disease. Curr. Top. Microbiol. Immunol. 310 (2006), 211–250.
Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Schwikowski, B., Ideker, T., Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13 (2003), 2498–2504.
Shao, W., Pedrioli, P.G.A., Wolski, W., Scurtescu, C., Schmid, E., Vizcaíno, J.A., Courcelles, M., Schuster, H., Kowalewski, D., Marino, F., et al. The SysteMHC Atlas project. Nucleic Acids Res. 46:D1 (2018), D1237–D1247.
Shlush, L.I., Mitchell, A., Heisler, L., Abelson, S., Ng, S.W.K., Trotman-Grant, A., Medeiros, J.J.F., Rao-Bhatia, A., Jaciw-Zurakowsky, I., Marke, R., et al. Tracing the origins of relapse in acute myeloid leukaemia to stem cells. Nature 547 (2017), 104–108.
Smart, A.C., Margolis, C.A., Pimentel, H., He, M.X., Miao, D., Adeegbe, D., Fugmann, T., Wong, K.-K., Van Allen, E.M., Intron retention is a source of neoepitopes in cancer. Nat. Biotechnol. 36 (2018), 1056–1058.
Smith, C.C., Selitsky, S.R., Chai, S., Armistead, P.M., Vincent, B.G., Serody, J.S., Alternative tumour-specific antigens. Nat. Rev. Cancer 19 (2019), 465–478.
Springer, I., Besser, H., Tickotsky-Moskovitz, N., Dvorkin, S., Louzoun, Y., Prediction of Specific TCR-Peptide Binding From Large Dictionaries of TCR-Peptide Pairs. Front. Immunol., 11, 2020, 1803.
Szolek, A., Schubert, B., Mohr, C., Sturm, M., Feldhahn, M., Kohlbacher, O., OptiType: precision HLA typing from next-generation sequencing data. Bioinformatics 30 (2014), 3310–3316.
Takahashi, N., Coluccio, A., Thorball, C.W., Planet, E., Shi, H., Offner, S., Turelli, P., Imbeault, M., Ferguson-Smith, A.C., Trono, D., ZNF445 is a primary regulator of genomic imprinting. Genes Dev. 33 (2019), 49–54.
Tamura, H., Dan, K., Tamada, K., Nakamura, K., Shioi, Y., Hyodo, H., Wang, S.D., Dong, H., Chen, L., Ogata, K., Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia. Clin. Cancer Res. 11 (2005), 5708–5717.
Tate, J.G., Bamford, S., Jubb, H.C., Sondka, Z., Beare, D.M., Bindal, N., Boutselakis, H., Cole, C.G., Creatore, C., Dawson, E., et al. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 47:D1 (2019), D941–D947.
Thomsen, M., Lundegaard, C., Buus, S., Lund, O., Nielsen, M., MHCcluster, a method for functional clustering of MHC molecules. Immunogenetics 65 (2013), 655–665.
Toffalori, C., Zito, L., Gambacorta, V., Riba, M., Oliveira, G., Bucci, G., Barcella, M., Spinelli, O., Greco, R., Crucitti, L., et al. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat. Med. 25 (2019), 603–611.
Tripathi, S.C., Peters, H.L., Taguchi, A., Katayama, H., Wang, H., Momin, A., Jolly, M.K., Celiktas, M., Rodriguez-Canales, J., Liu, H., et al. Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc. Natl. Acad. Sci. USA 113 (2016), E1555–E1564.
van der Lee, D.I., Reijmers, R.M., Honders, M.W., Hagedoorn, R.S., de Jong, R.C., Kester, M.G., van der Steen, D.M., de Ru, A.H., Kweekel, C., Bijen, H.M., et al. Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia. J. Clin. Invest. 129 (2019), 774–785.
Vasu, S., Kohlschmidt, J., Mrózek, K., Eisfeld, A.K., Nicolet, D., Sterling, L.J., Becker, H., Metzeler, K.H., Papaioannou, D., Powell, B.L., et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv. 2 (2018), 1645–1650.
Vizcaíno, J.A., Csordas, A., del-Toro, N., Dianes, J.A., Griss, J., Lavidas, I., Mayer, G., Perez-Riverol, Y., Reisinger, F., Ternent, T., et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 44:D1 (2016), D447–D456.
Wang, E., Lu, S.X., Pastore, A., Chen, X., Imig, J., Chun-Wei Lee, S., Hockemeyer, K., Ghebrechristos, Y.E., Yoshimi, A., Inoue, D., et al. Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia. Cancer Cell 35 (2019), 369–384.e7.
Wang, Q., Ding, H., He, Y., Li, X., Cheng, Y., Xu, Q., Yang, Y., Liao, G., Meng, X., Huang, C., Li, J., NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma. Cancer Lett. 444 (2019), 9–19.
Whiteway, A., Corbett, T., Anderson, R., Macdonald, I., Prentice, H.G., Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission. Br. J. Haematol. 120 (2003), 442–451.
Wilson, C.S., Davidson, G.S., Martin, S.B., Andries, E., Potter, J., Harvey, R., Ar, K., Xu, Y., Kopecky, K.J., Ankerst, D.P., et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 108 (2006), 685–696.
Wölfl, M., Greenberg, P.D., Antigen-specific activation and cytokine-facilitated expansion of naive, human CD8+ T cells. Nat Protoc 9 (2014), 950–966.
Wong, J.J.L., Gao, D., Nguyen, T.V., Kwok, C.-T., van Geldermalsen, M., Middleton, R., Pinello, N., Thoeng, A., Nagarajah, R., Holst, J., et al. Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment. Nat. Commun., 8, 2017, 15134.
Wu, T.D., Nacu, S., Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics 26 (2010), 873–881.
Yang, L., Rau, R., Goodell, M.A., DNMT3A in haematological malignancies. Nat. Rev. Cancer 15 (2015), 152–165.
Yang, X., Lu, B., Sun, X., Han, C., Fu, C., Xu, K., Wang, M., Li, D., Chen, Z., Opal, P., et al. ANP32A regulates histone H3 acetylation and promotes leukemogenesis. Leukemia 32 (2018), 1587–1597.
Zhang, J., Hu, X., Wang, J., Sahu, A.D., Cohen, D., Song, L., Ouyang, Z., Fan, J., Wang, B., Fu, J., et al. Immune receptor repertoires in pediatric and adult acute myeloid leukemia. Genome Med., 11, 2019, 73.
Zhang, X., Dong, W., Zhou, H., Li, H., Wang, N., Miao, X., Jia, L., α-2,8-Sialyltransferase Is Involved in the Development of Multidrug Resistance via PI3K/Akt Pathway in Human Chronic Myeloid Leukemia. IUBMB Life 67 (2015), 77–87.
Zhao, Q., Laverdure, J.P., Lanoix, J., Durette, C., Côté, C., Bonneil, É., Laumont, C.M., Gendron, P., Vincent, K., Courcelles, M., et al. Proteogenomics Uncovers a Vast Repertoire of Shared Tumor-Specific Antigens in Ovarian Cancer. Cancer Immunol. Res. 8 (2020), 544–555.
Zhi, H., Ning, S., Li, X., Li, Y., Wu, W., Li, X., A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers. Nucleic Acids Res. 42 (2014), 8258–8270.
Zhou, J., Chng, W.J., Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia. Stem Cell Investig., 4, 2017, 6.
Zhou, Y., Lu, Y., Tian, W., Epigenetic features are significantly associated with alternative splicing. BMC Genomics, 13, 2012, 123.