Impact of MHC-II on the Prognosis and Treatment of Acute Myeloid Leukemia: A WGCNA Analysis
Abstract
prevalent forms of leukemia in adults. Investigating the molecular mechanisms that influence the prognosis of AML holds great promise for
the development of novel therapeutic strategies. In this study, we categorized patients into high- and low-prognosis groups based on survival
data from the TCGA dataset. To further explore the molecular underpinnings, we performed enrichment analysis using Gene Ontology (GO)
and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, we conducted Weighted Gene Co-expression Network Analysis
(WGCNA) and protein-protein interaction (PPI) analysis to identify 10 key prognostic genes. Subsequently, we used the L1000FWD application to screen for potential small molecule drug candidates targeting these key genes, leading to the identification of BI-2536. Molecular
docking validation confirmed its binding potential. Our results revealed that HLA-DRA, HLA-DPA1, HLA-DRB1, CD74, HLA-DMB, HLADPB1, HLA-DMA, HLA-DRB5, HLA-DQB2, and HLA-DQB1 are crucial prognostic biomarkers for AML.
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[1] Dhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep 17;373(12):1136-52.
[2] James RF, Edwards S, Hui KM, Bassett PD, Grosveld F. The effect of class II gene transfection on the tumourigenicity of the H-2Knegative mouse leukaemia cell line K36.16. Immunology. 1991 Feb;72(2):213-8.
[3] Oh DY, Kwek SS, Raju SS, Li T, McCarthy E, Chow E, Aran D, Ilano A, Pai CS, Rancan C, Allaire K, Burra A, Sun Y, Spitzer MH,
Mangul S, Porten S, Meng MV, Friedlander TW, Ye CJ, Fong L. Intratumoral CD4+T Cells Mediate Anti-tumor Cytotoxicity in Human
Bladder Cancer. Cell. 2020 Jun 25;181(7):1612-1625.e13.
[4] Alspach E, Lussier DM, Miceli AP, Kizhvatov I, DuPage M, Luoma AM, Meng W, Lichti CF, Esaulova E, Vomund AN, Runci D, Ward
JP, Gubin MM, Medrano RFV, Arthur CD, White JM, Sheehan KCF, Chen A, Wucherpfennig KW, Jacks T, Unanue ER, Artyomov MN,
Schreiber RD. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature. 2019 Oct;574(7780):696-701.
[5] Ho JNHG, Schmidt D, Lowinus T, Ryoo J, Dopfer EP, Gonzalo Nez N, Costa-Pereira S, Toffalori C, Punta M, Fetsch V, Wertheimer T,
Rittmann MC, Braun LM, Follo M, Briere C, Vinnakota JM, Langenbach M, Koppers F, Shoumariyeh K, Engel H, Rckert T, Mrklin M,
Holzmayer S, Illert AL, Magon F, Andrieux G, Duquesne S, Pfeifer D, Staniek J, Rizzi M, Miething C, Khler N, Duyster J, Menssen
HD, Boerries M, Buescher JM, Cabezas-Wallscheid N, Blazar BR, Apostolova P, Vago L, Pearce EL, Becher B, Zeiser R. Targeting
MDM2 enhances antileukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation. Blood. 2022 Sep
8;140(10):1167-1181.
[6] Vago L, Gojo I. Immune escape and immunotherapy of acute myeloid leukemia. J Clin Invest. 2020 Apr 1;130(4):1552-1564.
[7] D. Santesmasses, M. Mariotti, V.N. Gladyshev, Bioinformatics of selenoproteins, Antioxid. Redox Signal. 33 (7) (2020) 525536.
[8] X. Huang, S. Liu, L. Wu, M. Jiang, Y. Hou, High throughput single cell RNA sequencing, bioinformatics analysis and applications, Adv.
Exp. Med. Biol. 1068 (2018) 3343.
[9] Vincent KM, Findlay SD, Postovit LM. Assessing breast cancer cell lines as tumour models by comparison of mRNA expression profiles. Breast Cancer Res. 2015 Aug 20;17(1):114.
[10] Wang Z, Lachmann A, Keenan AB, Ma'ayan A. L1000FWD: fireworks visualization of drug-induced transcriptomic signatures. Bioinformatics. 2018 Jun 15;34(12):2150-2152.
[11] Morris GM, Huey R, Olson AJ: Using AutoDock for ligand-receptor docking. Curr Protoc Bioinformatics 2008, Chapter 8:Unit 8.14.
[12] Wang Y, Bryant SH, Cheng T, Wang J, Gindulyte A, Shoemaker BA, Thiessen PA, He S, Zhang J: PubChem BioAssay: 2017 update.
Nucleic Acids Res 2017, 45:D955-d963.
[13] Liu H. Emerging agents and regimens for AML. J Hematol Oncol. 2021 Mar 23;14(1):49.
[14] Passweg JR, Baldomero H, Basak GW, Chabannon C, Corbacioglu S, Duarte R, et al. The EBMT activity survey report 2017: a focus on
allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies. Bone Marrow Transplant. 2019;54(10):1575
1585.
[15] Sauerer T, Velzquez GF, Schmid C. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: immune escape
mechanisms and current implications for therapy. Mol Cancer. 2023 Nov 11;22(1):180.
[16] DeWolf S, Tallman MS. How I treat relapsed or refractory AML. Blood. 2020 Aug 27;136(9):1023-1032.
[17] Arfons LM, Tomblyn M, Rocha V, Lazarus HM. Second hematopoietic stem cell transplantation in myeloid malignancies. Curr Opin
Hematol. 2009;16(2):112123.
[18] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
[19] Breems DA, Van Putten WL, Huijgens PC, et al.. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin
Oncol. 2005;23(9):1969-1978.
[20] Ganzel C, Sun Z, Cripe LD, et al.. Very poor long-term survival in past and more recent studies for relapsed AML patients: the ECOGACRIN experience. Am J Hematol. 2018;93(8):1074-1081.
[21] Z. Tian, W. He, J. Tang, X. Liao, Q. Yang, Y. Wu, et al., Identification of important modules and biomarkers in breast cancer based on
WGCNA, Onco. Targets. Ther.13 (2020) 68056817.
[22] Li X, Zhou H, Ma R, Guo W, Yang X, Li X, Liu Z, Zhong Y, Jing Z. Structure of POU2AF1 recombinant protein and it affects the
progression and treatment of liver cancer based on WGCNA and molecular docking analysis. Int J Biol Macromol. 2024 Oct;278(Pt
1):134629.
[23] Perry JS, Hsieh CS. Development of T-cell tolerance utilizes both cell-autonomous and cooperative presentation of self-antigen. Immunol Rev. 2016 May;271(1):141-55.
[24] van der Merwe PA, Davis SJ. Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol. 2003;21:659-84.
[25] Starlets D, Gore Y, Binsky I, Haran M, Harpaz N, Shvidel L, Becker-Herman S, Berrebi A, Shachar I. Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival.
[26] Borghese F, Clanchy FI. CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease. Expert Opin Ther
Targets. 2011 Mar;15(3):237-51.
[27] Long EO, Strubin M, Wake CT, Gross N, Carrel S, Goodfellow P, Accolla RS, Mach B. Isolation of cDNA clones for the p33 invariant
chain associated with HLA-DR antigens. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5714-8.
[28] Sauerer T, Velzquez GF, Schmid C. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: immune escape
mechanisms and current implications for therapy. Mol Cancer. 2023 Nov 11;22(1):180.
[29] Wang Y, Bin T, Tang J, Xu XJ, Lin C, Lu B, Sun TT. Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes. Front Immunol. 2023 Nov 22;14:1268090.
[30] Nelde A, Schuster H, Heitmann JS, Bauer J, Maringer Y, Zwick M, Volkmer JP, Chen JY, Stanger AMP, Lehmann A, Appiah B, Mrklin M,
Rcker-Braun E, Salih HR, Roerden M, Schroeder SM, Hring MF, Schlosser A, Schetelig J, Schmitz M, Boerries M, Khler N, Lengerke C, Majeti R, Weissman IL, Rammensee HG, Walz JS. Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLAPresented Antigens on Leukemia Progenitor Cells. Blood Cancer Discov. 2023 Nov 1;4(6):468-489.
DOI: http://dx.doi.org/10.70711/mhr.v3i2.9470
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