Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
18
06
2023
accepted:
29
11
2023
revised:
27
11
2023
medline:
13
12
2023
pubmed:
13
12
2023
entrez:
12
12
2023
Statut:
aheadofprint
Résumé
AML with chromosomal alterations involving 3q26 overexpresses the transcription factor (TF) EVI1, associated with therapy refractoriness and inferior overall survival in AML. Consistent with a CRISPR screen highlighting BRD4 dependency, treatment with BET inhibitor (BETi) repressed EVI1, LEF1, c-Myc, c-Myb, CDK4/6, and MCL1, and induced apoptosis of AML cells with 3q26 lesions. Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear β-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, GATA2 and MECOM loci, abolished interactions between MYC enhancers, repressing AML stemness while upregulating mRNA gene-sets of interferon/inflammatory response, TGF-β signaling and apoptosis-regulation. Co-treatment with TV and BETi or venetoclax induced synergistic in vitro lethality and reduced AML burden, improving survival of NSG mice harboring xenografts of AML with 3q26.2 lesions.
Identifiants
pubmed: 38086946
doi: 10.1038/s41375-023-02108-3
pii: 10.1038/s41375-023-02108-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Birdwell C, Fiskus W, Kadia TM, DiNardo CD, Mill CP, Bhalla KN. EVI1 dysregulation: impact on biology and therapy of myeloid malignancies. Blood Cancer J. 2021;11:64.
pubmed: 33753715
pmcid: 7985498
doi: 10.1038/s41408-021-00457-9
Morishita K, Parker DS, Mucenski ML, Jenkins NA, Copeland NG, Ihle JN. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Cell. 1988;54:831–40.
pubmed: 2842066
doi: 10.1016/S0092-8674(88)91175-0
Perkins AS, Fishel R, Jenkins NA, Copeland NG. Evi-1: a murine zinc finger proto-oncogene, encodes a sequence-specific DNA-binding protein. Mol Cell Biol. 1991;11:2665–74.
pubmed: 2017172
pmcid: 360036
Delwel R, Funabiki T, Kreider BL, Morishita K, Ihle JN. Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. Mol Cell Biol. 1993;13:4291–300.
pubmed: 8321231
pmcid: 359982
Zhang Y, Stehling-Sun S, Lezon-Geyda K, Juneja SC, Coillard L, Chatterjee G, et al. PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function. Blood. 2011;118:3853–61.
pubmed: 21666053
pmcid: 3193263
doi: 10.1182/blood-2011-02-334680
Kataoka K, Sato T, Yoshimi A, Goyama S, Tsuruta T, Kobayashi H, et al. Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med. 2011;208:2403–16.
pubmed: 22084405
pmcid: 3256960
doi: 10.1084/jem.20110447
Du Y, Jenkins NA, Copeland NG. Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells. Blood. 2005;106:3932–9.
pubmed: 16109773
pmcid: 1895096
doi: 10.1182/blood-2005-03-1113
Morishita K, Parganas E, Matsugi T, Ihle JN. Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor. Mol Cell Biol. 1992;12:183–9.
pubmed: 1370341
pmcid: 364082
Steinleitner K, Rampetsreiter P, Köffel R, Ramanathan G, Mannhalter C, Strobl H, et al. EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages. Anticancer Res. 2012;32:4883–9.
pubmed: 23155256
pmcid: 3605800
Wilson M, Tsakraklides V, Tran M, Xiao YY, Zhang Y, Perkins AS. EVI1 interferes with myeloid maturation via transcriptional repression of Cebpa, via binding to two far downstream regulatory elements. J Biol Chem. 2016;291:13591–607.
pubmed: 27129260
pmcid: 4919445
doi: 10.1074/jbc.M115.708156
Cai SF, Chu SH, Goldberg AD, Parvin S, Koche RP, Glass JL, et al. Leukemia cell of origin influences apoptotic priming and sensitivity to LSD1 inhibition. Cancer Discov. 2020;10:1500–13.
pubmed: 32606137
pmcid: 7584353
doi: 10.1158/2159-8290.CD-19-1469
Senyuk V, Sinha KK, Li D, Rinaldi CR, Yanamandra S, Nucifora G. Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis. Cancer Res. 2007;67:5658–66.
pubmed: 17575132
doi: 10.1158/0008-5472.CAN-06-3962
Kreider BL, Orkin SH, Ihle JN. Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. Proc Natl Acad Sci USA. 1993;90:6454–8.
pubmed: 8341654
pmcid: 46950
doi: 10.1073/pnas.90.14.6454
Laricchia-Robbio L, Premanand K, Rinaldi CR, Nucifora G. EVI1 Impairs myelopoiesis by deregulation of PU.1 function. Cancer Res. 2009;69:1633–42.
pubmed: 19208846
doi: 10.1158/0008-5472.CAN-08-2562
Ayoub E, Wilson MP, McGrath KE, Li AJ, Frisch BJ, Palis J, et al. EVI1 overexpression reprograms hematopoiesis via upregulation of Spi1 transcription. Nat Commun. 2018;9:4239.
pubmed: 30315161
pmcid: 6185954
doi: 10.1038/s41467-018-06208-y
Hinai AA, Valk PJ. Review: Aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2016;172:870–8.
pubmed: 26729571
doi: 10.1111/bjh.13898
Ottema S, Mulet-Lazaro R, Beverloo HB, Erpelinck CAJ, van Herk S, Helm RV, et al. Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. Blood. 2020;136:224–34.
pubmed: 32219447
doi: 10.1182/blood.2019003701
Groschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BAM, Erpelinck C, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157:369–81.
pubmed: 24703711
doi: 10.1016/j.cell.2014.02.019
Yamazaki H, Suzuki M, Otsuki A, Shimizu R, Bresnick EH, Engel JD, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25:415–27.
pubmed: 24703906
pmcid: 4012341
doi: 10.1016/j.ccr.2014.02.008
Ottema S, Mulet-Lazaro R, Erpelinck-Verschueren C, van Herk S, Havermans M, Arricibita Varea A, et al. The leukemic oncogene EVI1 hijacks a MYC super-enhancer by CTCF-facilitated loops. Nat Commun. 2021;12:5679.
pubmed: 34584081
pmcid: 8479123
doi: 10.1038/s41467-021-25862-3
Katayama S, Suzuki M, Yamaoka A, Keleku-Lukwete N, Katsuoka F, Otsuki A, et al. GATA2 haploinsufficiency accelerates EVI1-driven leukemogenesis. Blood. 2017;130:908–19.
pubmed: 28630119
doi: 10.1182/blood-2016-12-756767
Yamaoka A, Suzuki M, Katayama S, Orihara D, Engel JD, Yamamoto M. EVI1 and GATA2 misexpression induced by inv(3)(q21q26) contribute to megakaryocyte-lineage skewing and leukemogenesis. Blood Adv. 2020;4:1722–36.
pubmed: 32330245
pmcid: 7189294
doi: 10.1182/bloodadvances.2019000978
Sun J, Konoplev SN, Wang X, Cui W, Chen SS, Medeiros LJ, et al. De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification. Mod Pathol. 2011;24:384–9.
pubmed: 21113141
doi: 10.1038/modpathol.2010.210
Lugthart S, Gröschel S, Beverloo HB, Kayser S, Valk PJ, van Zelderen-Bhola SL, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol. 2010;28:3890–8.
pubmed: 20660833
doi: 10.1200/JCO.2010.29.2771
Sitges M, Boluda B, Garrido A, Morgades M, Granada I, Barragan E, et al. Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols. Eur J Haematol. 2020;105:138–47.
pubmed: 32243655
doi: 10.1111/ejh.13417
Richard-Carpentier G, Rausch CR, Sasaki K, Hammond D, Morita K, Takahashi K, et al. Characteristics and clinical outcomes of patients with acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). Haematologica. 2023;108:2331–42.
pubmed: 36951163
pmcid: 10483357
Schmoellerl J, Barbosa IAM, Minnich M, Andersch F, Smeenk L, Havermans M, et al. EVI1 drives leukemogenesis through aberrant ERG activation. Blood. 2023;141:453–66.
pubmed: 36095844
doi: 10.1182/blood.2022016592
Glass C, Wuertzer C, Cui X, Bi Y, Davuluri R, Xiao YY, et al. Global identification of EVI1 target genes in acute myeloid leukemia. PLoS One. 2013;8:e67134.
pubmed: 23826213
pmcid: 3694976
doi: 10.1371/journal.pone.0067134
Pradhan AK, Mohapatra AD, Nayak KB, Chakraborty S. Acetylation of the proto-oncogene EVI1 abrogates Bcl-xL promoter binding and induces apoptosis. PLoS One. 2011;6:e25370.
pubmed: 21980434
pmcid: 3182211
doi: 10.1371/journal.pone.0025370
Buonamici S, Li D, Chi Y, Zhao R, Wang X, Brace L, et al. EVI1 induces myelodysplastic syndrome in mice. J Clin Invest. 2004;114:713–9.
pubmed: 15343390
pmcid: 514587
doi: 10.1172/JCI21716
Groschel S, Sanders MA, Hoogenboezem R, Zeilemaker A, Havermans M, Erpelinck C, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125:133–9.
pubmed: 25381062
pmcid: 4334729
doi: 10.1182/blood-2014-07-591461
Tanaka A, Nakano TA, Nomura M, Yamazaki H, Bewersdorf JP, Mulet-Lazaro R, et al. Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. Blood. 2022;140:875–88.
pubmed: 35709354
pmcid: 9412007
doi: 10.1182/blood.2021015325
Lavallee VP, Gendron P, Lemieux S, D’Angelo G, Hebert J, Sauvageau G. EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations. Blood. 2015;125:140–3.
pubmed: 25331116
pmcid: 4358966
doi: 10.1182/blood-2014-07-591529
Will B, Steidl U. Combinatorial haplo-deficient tumor suppression in 7q-deficient myelodysplastic syndrome and acute myeloid leukemia. Cancer Cell. 2014;25:555–7.
pubmed: 24823633
doi: 10.1016/j.ccr.2014.04.018
Groschel S, Lugthart S, Schlenk RF, Valk PJ, Eiwen K, Goudswaard C, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28:2101–7.
pubmed: 20308656
doi: 10.1200/JCO.2009.26.0646
Manachai N, Saito Y, Nakahata S, Bahirvani AG, Osato M, Morishita K. Activation of EVI1 transcription by the LEF1/beta-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia. Biochem Biophys Res Commun. 2017;482:994–1000.
pubmed: 27908728
doi: 10.1016/j.bbrc.2016.11.146
Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351:657–67.
pubmed: 15306667
doi: 10.1056/NEJMoa040258
Saenz DT, Fiskus W, Manshouri T, Mill CP, Qian Y, Raina K, et al. Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML. Leukemia. 2019;33:1373–86.
pubmed: 30575820
doi: 10.1038/s41375-018-0334-3
Saenz DT, Fiskus W, Mill CP, Perera D, Manshouri T, Lara BH, et al. Mechanistic basis and efficacy of targeting the β-catenin-TCF7L2-JMJD6-c-Myc axis to overcome resistance to BET inhibitors. Blood. 2020;135:1255–69.
pubmed: 32068780
pmcid: 7146021
doi: 10.1182/blood.2019002922
Mill CP, Fiskus W, DiNardo CD, Qian Y, Raina K, Rajapakshe K, et al. RUNX1 targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood. 2019;134:59–73.
pubmed: 31023702
pmcid: 6609954
doi: 10.1182/blood.2018893982
Fiskus W, Saba N, Shen M, Ghias M, Liu J, Gupta SD, et al. Auranofin induces lethal oxidative and endoplasmic reticulum stress and exerts potent preclinical activity against chronic lymphocytic leukemia. Cancer Res. 2014;74:2520–32.
pubmed: 24599128
pmcid: 4172421
doi: 10.1158/0008-5472.CAN-13-2033
Fiskus W, Mill CP, Nabet B, Perera D, Birdwell C, Manshouri T, et al. Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells. Blood Cancer J. 2021;11:98.
pubmed: 34016956
pmcid: 8138012
doi: 10.1038/s41408-021-00487-3
Bagchi S, Fredriksson R, Wallén-Mackenzie Å. In situ Proximity Ligation Assay (PLA). Methods Mol Biol. 2015;1318:149–59.
pubmed: 26160573
doi: 10.1007/978-1-4939-2742-5_15
Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H. The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood. 2001;97:2815–22.
pubmed: 11313276
doi: 10.1182/blood.V97.9.2815
Elsayed AH, Rafiee R, Cao X, Raimondi S, Downing JR, Ribeiro R, et al. A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia. Leukemia. 2020;34:735–45.
pubmed: 31645648
doi: 10.1038/s41375-019-0604-8
Smeenk L, Ottema S, Mulet-Lazaro R, Ebert A, Havermans M, Varea AA, et al. Selective requirement of MYB for oncogenic hyperactivation of a translocated enhancer in leukemia. Cancer Discov. 2021;11:2868–83.
pubmed: 33980539
pmcid: 8563373
doi: 10.1158/2159-8290.CD-20-1793
Hnisz D, Schuijers J, Lin CY, Weintraub AS, Abraham BJ, Lee TI, et al. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. Mol Cell. 2015;58:362–70.
pubmed: 25801169
pmcid: 4402134
doi: 10.1016/j.molcel.2015.02.014
Saint-André V, Federation AJ, Lin CY, Abraham BJ, Reddy J, Lee TI, et al. Models of human core transcriptional regulatory circuitries. Genome Res. 2016;26:385–96.
pubmed: 26843070
pmcid: 4772020
doi: 10.1101/gr.197590.115
Jin L, Garcia J, Chan E, de la Cruz C, Segal E, Merchant M, et al. Therapeutic targeting of the CBP/p300 bromodomain blocks the growth of castration-resistant prostate cancer. Cancer Res. 2017;77:5564–75.
pubmed: 28819026
doi: 10.1158/0008-5472.CAN-17-0314
Short NJ, Konopleva M, Kadia TM, Borthakur G, Ravandi F, DiNardo CD, et al. Advances in the treatment of acute myeloid leukemia: new drugs and new challenges. Cancer Discov. 2020;10:506–25.
pubmed: 32014868
doi: 10.1158/2159-8290.CD-19-1011
Luskin MR, Murakami MA, Manalis SR, Weinstock DM. Targeting minimal residual disease: a path to cure? Nat Rev Cancer. 2018;18:255–63.
pubmed: 29376520
pmcid: 6398166
doi: 10.1038/nrc.2017.125