Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.
AML
Cytarabine
Resistance
SAMHD1
VLP
Vpx
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
13 Jul 2024
13 Jul 2024
Historique:
received:
04
04
2024
accepted:
02
07
2024
medline:
14
7
2024
pubmed:
14
7
2024
entrez:
13
7
2024
Statut:
epublish
Résumé
Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells.
Identifiants
pubmed: 39003408
doi: 10.1007/s10238-024-01425-w
pii: 10.1007/s10238-024-01425-w
doi:
Substances chimiques
Cytarabine
04079A1RDZ
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
SAMHD1 protein, human
EC 3.1.5.-
Viral Regulatory and Accessory Proteins
0
VPX protein, Human immunodeficiency virus 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155Subventions
Organisme : Wilhelm Sander-Stiftung
ID : 2020.097.1
Organisme : Wilhelm Sander-Stiftung
ID : 2020.097.1
Organisme : Fundação para a Ciência e Tecnologia
ID : DFA/BD/4965/2020
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB-TRR 388/1 2021-452881907
Informations de copyright
© 2024. The Author(s).
Références
American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML) 2023 [accessed 2023/11/30/]. Available from: https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html .
Lowenberg B, Rowe JM. Introduction to the review series on advances in acute myeloid leukemia (AML). Blood. 2016;127(1):1. https://doi.org/10.1182/blood-2015-10-662684 .
doi: 10.1182/blood-2015-10-662684
pubmed: 26660430
Fleischmann M, Schnetzke U, Hochhaus A, Scholl S. Management of acute myeloid leukemia: current treatment options and future perspectives. Cancers. 2021;13(22):5722. https://doi.org/10.3390/cancers13225722 .
doi: 10.3390/cancers13225722
pubmed: 34830877
pmcid: 8616498
Nair R, Salinas-Illarena A, Baldauf HM. New strategies to treat AML: novel insights into AML survival pathways and combination therapies. Leukemia. 2021;35(2):299–311. https://doi.org/10.1038/s41375-020-01069-1 .
doi: 10.1038/s41375-020-01069-1
pubmed: 33122849
de Leeuw DC, Ossenkoppele GJ, Janssen J. Older patients with acute myeloid leukemia deserve individualized treatment. Curr Oncol Rep. 2022;24(11):1387–400. https://doi.org/10.1007/s11912-022-01299-9 .
doi: 10.1007/s11912-022-01299-9
pubmed: 35653050
pmcid: 9606099
Schneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, et al. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nat Med. 2017;23(2):250–5. https://doi.org/10.1038/nm.4255 .
doi: 10.1038/nm.4255
pubmed: 27991919
Herold N, Rudd SG, Ljungblad L, Sanjiv K, Myrberg IH, Paulin CB, et al. Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies. Nat Med. 2017;23(2):256–63. https://doi.org/10.1038/nm.4265 .
doi: 10.1038/nm.4265
pubmed: 28067901
Oellerich T, Schneider C, Thomas D, Knecht KM, Buzovetsky O, Kaderali L, et al. Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML. Nat Commun. 2019;10(1):3475. https://doi.org/10.1038/s41467-019-11413-4 .
doi: 10.1038/s41467-019-11413-4
pubmed: 31375673
pmcid: 6677770
Rothenburger T, McLaughlin KM, Herold T, Schneider C, Oellerich T, Rothweiler F, et al. SAMHD1 is a key regulator of the lineage-specific response of acute lymphoblastic leukaemias to nelarabine. Commun Biol. 2020;3(1):324. https://doi.org/10.1038/s42003-020-1052-8 .
doi: 10.1038/s42003-020-1052-8
pubmed: 32581304
pmcid: 7314829
Xagoraris I, Vassilakopoulos TP, Drakos E, Angelopoulou MK, Panitsas F, Herold N, et al. Expression of the novel tumour suppressor sterile alpha motif and HD domain-containing protein 1 is an independent adverse prognostic factor in classical Hodgkin lymphoma. Br J Haematol. 2021;193(3):488–96. https://doi.org/10.1111/bjh.17352 .
doi: 10.1111/bjh.17352
pubmed: 33528031
Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, et al. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature. 2011;480(7377):379–82. https://doi.org/10.1038/nature10623 .
doi: 10.1038/nature10623
pubmed: 22056990
Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, et al. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature. 2011;474(7353):658–61. https://doi.org/10.1038/nature10195 .
doi: 10.1038/nature10195
pubmed: 21720370
pmcid: 3179858
Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Ségéral E, et al. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature. 2011;474(7353):654–7. https://doi.org/10.1038/nature10117 .
doi: 10.1038/nature10117
pubmed: 21613998
pmcid: 3595993
Lim ES, Fregoso OI, McCoy CO, Matsen FA, Malik HS, Emerman M. The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. Cell Host Microbe. 2012;11(2):194–204. https://doi.org/10.1016/j.chom.2012.01.004 .
doi: 10.1016/j.chom.2012.01.004
pubmed: 22284954
pmcid: 3288607
Zeltins A. Construction and characterization of virus-like particles: a review. Mol Biotechnol. 2013;53(1):92–107. https://doi.org/10.1007/s12033-012-9598-4 .
doi: 10.1007/s12033-012-9598-4
pubmed: 23001867
Nooraei S, Bahrulolum H, Hoseini ZS, Katalani C, Hajizade A, Easton AJ, et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnol. 2021;19(1):59. https://doi.org/10.1186/s12951-021-00806-7 .
doi: 10.1186/s12951-021-00806-7
Tariq H, Batool S, Asif S, Ali M, Abbasi BH. Virus-like particles: revolutionary platforms for developing vaccines against emerging infectious diseases. Front Microbiol. 2021;12:790121. https://doi.org/10.3389/fmicb.2021.790121 .
doi: 10.3389/fmicb.2021.790121
pubmed: 35046918
Gramberg T, Sunseri N, Landau NR. Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx. J Virol. 2010;84(3):1387–96. https://doi.org/10.1128/jvi.01437-09 .
doi: 10.1128/jvi.01437-09
pubmed: 19923175
Nair R, Pignot Y, Salinas-Illarena A, Barreiter VA, Wratil PR, Keppler OT, et al. Purified recombinant lentiviral Vpx proteins maintain their SAMHD1 degradation efficiency in resting CD4(+) T cells. Anal Biochem. 2023;670:115153. https://doi.org/10.1016/j.ab.2023.115153 .
doi: 10.1016/j.ab.2023.115153
pubmed: 37037311
Vermeire J, Naessens E, Vanderstraeten H, Landi A, Iannucci V, Van Nuffel A, et al. Quantification of reverse transcriptase activity by real-time PCR as a fast and accurate method for titration of HIV, lenti- and retroviral vectors. PLoS ONE. 2012;7(12):e50859. https://doi.org/10.1371/journal.pone.0050859 .
doi: 10.1371/journal.pone.0050859
pubmed: 23227216
pmcid: 3515444
Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, et al. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Nat Med. 2012;18(11):1682–7. https://doi.org/10.1038/nm.2964 .
doi: 10.1038/nm.2964
pubmed: 22972397
Krupka C, Kufer P, Kischel R, Zugmaier G, Bögeholz J, Köhnke T, et al. CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood. 2014;123(3):356–65. https://doi.org/10.1182/blood-2013-08-523548 .
doi: 10.1182/blood-2013-08-523548
pubmed: 24300852
Cavrois M, De Noronha C, Greene WC. A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes. Nat Biotechnol. 2002;20(11):1151–4. https://doi.org/10.1038/nbt745 .
doi: 10.1038/nbt745
pubmed: 12355096
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–9. https://doi.org/10.1038/s41586-021-03819-2 .
doi: 10.1038/s41586-021-03819-2
pubmed: 34265844
pmcid: 8371605
Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, et al. AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 2021;50(D1):D439–44. https://doi.org/10.1093/nar/gkab1061 .
doi: 10.1093/nar/gkab1061
pmcid: 8728224
Goddard TD, Huang CC, Meng EC, Pettersen EF, Couch GS, Morris JH, et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 2018;27(1):14–25. https://doi.org/10.1002/pro.3235 .
doi: 10.1002/pro.3235
pubmed: 28710774
Pettersen EF, Goddard TD, Huang CC, Meng EC, Couch GS, Croll TI, et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 2021;30(1):70–82. https://doi.org/10.1002/pro.3943 .
doi: 10.1002/pro.3943
pubmed: 32881101
Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: making protein folding accessible to all. Nat Methods. 2022;19(6):679–82. https://doi.org/10.1038/s41592-022-01488-1 .
doi: 10.1038/s41592-022-01488-1
pubmed: 35637307
pmcid: 9184281
Baldauf HM, Stegmann L, Schwarz SM, Ambiel I, Trotard M, Martin M, et al. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells. Proc Natl Acad Sci USA. 2017;114(10):2729–34. https://doi.org/10.1073/pnas.1613635114 .
doi: 10.1073/pnas.1613635114
pubmed: 28228523
pmcid: 5347584
Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J. The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP. J Biol Chem. 1998;273(50):33414–22. https://doi.org/10.1074/jbc.273.50.33414 .
doi: 10.1074/jbc.273.50.33414
pubmed: 9837918
Faust TB, Binning JM, Gross JD, Frankel AD. Making sense of multifunctional proteins: human immunodeficiency virus Type 1 accessory and regulatory proteins and connections to transcription. Annu Rev Virol. 2017;4(1):241–60. https://doi.org/10.1146/annurev-virology-101416-041654 .
doi: 10.1146/annurev-virology-101416-041654
pubmed: 28961413
pmcid: 5750048
Grewe B, Ehrhardt K, Hoffmann B, Blissenbach M, Brandt S, Uberla K. The HIV-1 Rev protein enhances encapsidation of unspliced and spliced, RRE-containing lentiviral vector RNA. PLoS ONE. 2012;7(11):e48688. https://doi.org/10.1371/journal.pone.0048688 .
doi: 10.1371/journal.pone.0048688
pubmed: 23133650
pmcid: 3486793
Selig L, Pages JC, Tanchou V, Prévéral S, Berlioz-Torrent C, Liu LX, et al. Interaction with the p6 domain of the gag precursor mediates incorporation into virions of Vpr and Vpx proteins from primate lentiviruses. J Virol. 1999;73(1):592–600. https://doi.org/10.1128/jvi.73.1.592-600.1999 .
doi: 10.1128/jvi.73.1.592-600.1999
pubmed: 9847364
pmcid: 103865
Anderson MG, Clements JE. Two strains of SIVmac show differential transactivation mediated by sequences in the promoter. Virology. 1992;191(2):559–68. https://doi.org/10.1016/0042-6822(92)90231-d .
doi: 10.1016/0042-6822(92)90231-d
pubmed: 1448914
Batten CJ, De Rose R, Wilson KM, Agy MB, Chea S, Stratov I, et al. Comparative evaluation of simian, simian-human, and human immunodeficiency virus infections in the pigtail macaque (Macaca nemestrina) model. AIDS Res Hum Retroviruses. 2006;22(6):580–8. https://doi.org/10.1089/aid.2006.22.580 .
doi: 10.1089/aid.2006.22.580
pubmed: 16796533
Schwefel D, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, et al. Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx. Cell Host Microbe. 2015;17(4):489–99. https://doi.org/10.1016/j.chom.2015.03.004 .
doi: 10.1016/j.chom.2015.03.004
pubmed: 25856754
pmcid: 4400269
Floeth M, Elges S, Gerss J, Schwöppe C, Kessler T, Herold T, et al. Low-density lipoprotein receptor (LDLR) is an independent adverse prognostic factor in acute myeloid leukaemia. Br J Haematol. 2021;192(3):494–503. https://doi.org/10.1111/bjh.16853 .
doi: 10.1111/bjh.16853
pubmed: 32511755
Dobson CS, Reich AN, Gaglione S, Smith BE, Kim EJ, Dong J, et al. Antigen identification and high-throughput interaction mapping by reprogramming viral entry. Nat Methods. 2022;19(4):449–60. https://doi.org/10.1038/s41592-022-01436-z .
doi: 10.1038/s41592-022-01436-z
pubmed: 35396484
pmcid: 9012700
Mitchell K, Steidl U. Targeting immunophenotypic markers on leukemic stem cells: how lessons from current approaches and advances in the leukemia stem cell (LSC) model can inform better strategies for treating acute myeloid leukemia (AML). Cold Spring Harb Perspect Med. 2020;10(1):a036251. https://doi.org/10.1101/cshperspect.a036251 .
doi: 10.1101/cshperspect.a036251
pubmed: 31451539
pmcid: 6938655
Haubner S, Perna F, Köhnke T, Schmidt C, Berman S, Augsberger C, et al. Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML. Leukemia. 2019;33(1):64–74. https://doi.org/10.1038/s41375-018-0180-3 .
doi: 10.1038/s41375-018-0180-3
pubmed: 29946192
Darwish NH, Sudha T, Godugu K, Elbaz O, Abdelghaffar HA, Hassan EE, et al. Acute myeloid leukemia stem cell markers in prognosis and targeted therapy: potential impact of BMI-1, TIM-3 and CLL-1. Oncotarget. 2016;7(36):57811–20. https://doi.org/10.18632/oncotarget.11063 .
doi: 10.18632/oncotarget.11063
pubmed: 27506934
pmcid: 5295391
Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6(1):201. https://doi.org/10.1038/s41392-021-00572-w .
doi: 10.1038/s41392-021-00572-w
pubmed: 34054126
pmcid: 8165101