Glycogen synthase kinase 3 (GSK-3) consists of two isoforms (α and β) that were originally linked to glucose metabolism regulation. However, GSK-3 is also involved in several signaling pathways controlling many different key functions in healthy cells. GSK-3 is a unique kinase in that its isoforms are constitutively active, while they are inactivated mainly through phosphorylation at Ser residues by a variety of upstream kinases. In the early 1990s, GSK-3 emerged as a key player in cancer cell pathophysiology. Since active GSK-3 promotes destruction of multiple oncogenic proteins (e.g., β-catenin, c-Myc, Mcl-1) it was considered to be a tumor suppressor. Accordingly, GSK-3 is frequently inactivated in human cancer via aberrant regulation of upstream signaling pathways. More recently, however, it has emerged that GSK-3 isoforms display also oncogenic properties, as they up-regulate pathways critical for neoplastic cell proliferation, survival, and drug-resistance. The regulatory roles of GSK-3 isoforms in cell cycle, apoptosis, DNA repair, tumor metabolism, invasion, and metastasis reflect the therapeutic relevance of these kinases and provide the rationale for combining GSK-3 inhibitors with other targeted drugs. Here, we discuss the multiple and often conflicting roles of GSK-3 isoforms in acute leukemias. We also review the current status of GSK-3 inhibitor development for innovative leukemia therapy.
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Yeaman SJ, Armstrong JL, Bonavaud SM, Poinasamy D, Pickersgill L, Halse R. Regulation of glycogen synthesis in human muscle cells. Biochem Soc Trans. 2001;29:537–41.
McCubrey JA, Rakus D, Gizak A, Steelman LS, Abrams SL, Lertpiriyapong K, et al. Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer. Biochim Biophys Acta. 2016;1863:2942–76.
Dey S, Brothag C, Vijayaraghavan S. Signaling enzymes required for sperm maturation and fertilization in mammals. Front Cell Dev Biol. 2019;7:341.
Ahmad F, Woodgett JR. Emerging roles of GSK-3α in pathophysiology: emphasis on cardio-metabolic disorders. Biochim Biophys Acta-Mol Cell Res. 2020;1867:118616.
Nagini S, Sophia J, Mishra R. Glycogen synthase kinases: moonlighting proteins with theranostic potential in cancer. Semin Cancer Biol. 2019;56:25–36.
Cole AR. GSK3 as a sensor determining cell fate in the brain. Front Mol Neurosci. 2012;5:4.
Cervello M, Augello G, Cusimano A, Emma MR, Balasus D, Azzolina A, et al. Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma. Adv Biol Regul. 2017;65:59–76.
Itoh S, Saito T, Hirata M, Ushita M, Ikeda T, Woodgett JR, et al. GSK-3α and GSK-3β proteins are involved in early stages of chondrocyte differentiation with functional redundancy through RelA protein phosphorylation. J Biol Chem. 2012;287:29227–36.
Kerkela R, Kockeritz L, Macaulay K, Zhou J, Doble BW, Beahm C, et al. Deletion of GSK-3β in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. J Clin Invest. 2008;118:3609–18.
Yang K, Chen Z, Gao J, Shi W, Li L, Jiang S, et al. The Key roles of GSK-3β in regulating mitochondrial activity. Cell Physiol Biochem. 2017;44:1445–59.
Bechard M, Dalton S. Subcellular localization of glycogen synthase kinase 3β controls embryonic stem cell self-renewal. Mol Cell Biol. 2009;29:2092–104.
Evangelisti C, Chiarini F, Paganelli F, Marmiroli S, Martelli AM. Crosstalks of GSK3 signaling with the mTOR network and effects on targeted therapy of cancer. Biochim Biophys Acta-Mol Cell Res. 2020;1867:118635.
Ignatz-Hoover JJ, Wang V, Mackowski NM, Roe AJ, Ghansah IK, Ueda M, et al. Aberrant GSK3β nuclear localization promotes AML growth and drug resistance. Blood Adv. 2018;2:2890–2903.
Hu Y, Gu X, Li R, Luo Q, Xu Y. Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells. J Exp Clin Cancer Res. 2010;29:154.
Goc A, Al-Husein B, Katsanevas K, Steinbach A, Lou U, Sabbineni H, et al. Targeting Src-mediated Tyr216 phosphorylation and activation of GSK-3 in prostate cancer cells inhibit prostate cancer progression in vitro and in vivo. Oncotarget. 2014;5:775–87.
Takahashi-Yanaga F, Shiraishi F, Hirata M, Miwa Y, Morimoto S, Sasaguri T. Glycogen synthase kinase-3β is tyrosine-phosphorylated by MEK1 in human skin fibroblasts. Biochem Biophys Res Commun. 2004;316:411–5.
Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, et al. Crystal structure of glycogen synthase kinase 3 β: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell. 2001;105:721–32.
Kaidanovich-Beilin O, Woodgett JR. GSK-3: functional Insights from Cell Biology and Animal Models. Front Mol Neurosci. 2011;4:40.
Chiara F, Rasola A. GSK-3 and mitochondria in cancer cells. Front Oncol. 2013;3:16.
Lambrecht C, Libbrecht L, Sagaert X, Pauwels P, Hoorne Y, Crowther J, et al. Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo. Oncogene. 2018;37:544–52.
Tang XL, Wang CN, Zhu XY, Ni X. Protein tyrosine phosphatase SHP-1 modulates osteoblast differentiation through direct association with and dephosphorylation of GSK3β. Mol Cell Endocrinol. 2017;439:203–12.
de Groot RP, Auwerx J, Bourouis M, Sassone-Corsi P. Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy. Oncogene. 1993;8:841–7.
Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK3β to the APC-β-catenin complex and regulation of complex assembly. Science. 1996;272:1023–6.
Diehl JA, Cheng M, Roussel MF, Sherr CJ. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998;12:3499–11.
Leis H, Segrelles C, Ruiz S, Santos M, Paramio JM. Expression, localization, and activity of glycogen synthase kinase 3β during mouse skin tumorigenesis. Mol Carcinog. 2002;35:180–5.
Tong J, Wang P, Tan S, Chen D, Nikolovska-Coleska Z, Zou F, et al. Mcl-1 degradation is required for targeted therapeutics to eradicate colon cancer cells. Cancer Res. 2017;77:2512–21.
Shin S, Wolgamott L, Yu Y, Blenis J, Yoon SO. Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation. Proc Natl Acad Sci USA. 2011;108:E1204–13.
Shin S, Wolgamott L, Tcherkezian J, Vallabhapurapu S, Yu Y, Roux PP, et al. Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1. Oncogene. 2014;33:1690–9.
Robertson H, Hayes JD, Sutherland C. A partnership with the proteasome; the destructive nature of GSK3. Biochem Pharm. 2018;147:77–92.
Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, et al. Structural basis for recruitment of glycogen synthase kinase 3β to the axin-APC scaffold complex. EMBO J. 2003;22:494–501.
Stamos JL, Weis WI. The β-catenin destruction complex. Cold Spring Harb Perspect Biol. 2013;5:a007898.
Jung YS, Park JI. Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex. Exp Mol Med. 2020;52:183–91.
McCubrey JA, Steelman LS, Bertrand FE, Davis NM, Abrams SL, Montalto G, et al. Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia. 2014;28:15–33.
Doble BW, Patel S, Wood GA, Kockeritz LK, Woodgett JR. Functional redundancy of GSK-3α and GSK-3β in Wnt/β-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell. 2007;12:957–71.
Wagner FF, Benajiba L, Campbell AJ, Weiwer M, Sacher JR, Gale JP, et al. Exploiting an Asp-Glu “switch” in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia. Sci Transl Med. 2018;10:eaam8460.
Kitanaka N, Hall FS, Uhl GR, Kitanaka J. Lithium pharmacology and a potential role of lithium on methamphetamine abuse and dependence. Curr Drug Res Rev. 2019;11:85–91.
Takahashi-Yanaga F. Activator or inhibitor? GSK-3 as a new drug target. Biochem Pharm. 2013;86:191–9.
Neumann T, Benajiba L, Goring S, Stegmaier K, Schmidt B. Evaluation of improved glycogen synthase kinase-3α inhibitors in models of acute myeloid leukemia. J Med Chem. 2015;58:8907–19.
Wang Y, Dou X, Jiang L, Jin H, Zhang L, Zhang L, et al. Discovery of novel glycogen synthase kinase-3α inhibitors: structure-based virtual screening, preliminary SAR and biological evaluation for treatment of acute myeloid leukemia. Eur J Med Chem. 2019;171:221–34.
Ding S, Wu TY, Brinker A, Peters EC, Hur W, Gray NS, et al. Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci USA. 2003;100:7632–7.
Jiang J, Zhao M, Zhang A, Yu M, Lin X, Wu M, et al. Characterization of a GSK-3 inhibitor in culture of human cord blood primitive hematopoietic cells. Biomed Pharmacother. 2010;64:482–6.
Tolosa E, Litvan I, Hoglinger GU, Burn D, Lees A, Andres MV, et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord. 2014;29:470–8.
Matsunaga S, Fujishiro H, Takechi H. Efficacy and safety of glycogen synthase kinase 3 inhibitors for Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2019;69:1031–9.
del Ser T, Steinwachs KC, Gertz HJ, Andres MV, Gomez-Carrillo B, Medina M, et al. Treatment of Alzheimer’s disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimers Dis. 2013;33:205–5.
Gray JE, Infante JR, Brail LH, Simon GR, Cooksey JF, Jones SF, et al. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin. Invest New Drugs. 2015;33:1187–96.
Ballin A, Lehman D, Sirota P, Litvinjuk U, Meytes D. Increased number of peripheral blood CD34+ cells in lithium-treated patients. Br J Haematol. 1998;100:219–21.
Boggs DR, Joyce RA. The hematopoietic effects of lithium. Semin Hematol. 1983;20:129–38.
Joyce RA. Sequential effects of lithium on haematopoiesis. Br J Haematol. 1984;56:307–21.
Luis TC, Ichii M, Brugman MH, Kincade P, Staal FJ. Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development. Leukemia. 2012;26:414–21.
Trowbridge JJ, Xenocostas A, Moon RT, Bhatia M. Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nat Med. 2006;12:89–98.
Holmes T, O’Brien TA, Knight R, Lindeman R, Shen S, Song E, et al. Glycogen synthase kinase-3β inhibition preserves hematopoietic stem cell activity and inhibits leukemic cell growth. Stem Cells. 2008;26:1288–97.
Li J, Zhang L, Yin L, Ma N, Wang T, Wu Y, et al. In vitro expansion of hematopoietic stem cells by inhibition of both GSK3 and p38 signaling. Stem Cells Dev. 2019;28:1486–97.
Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12:446–51.
Huang J, Zhang Y, Bersenev A, O’Brien WT, Tong W, Emerson SG, et al. Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice. J Clin Invest. 2009;119:3519–29.
Huang J, Nguyen-McCarty M, Hexner EO, Danet-Desnoyers G, Klein PS. Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways. Nat Med. 2012;18:1778–85.
Guezguez B, Almakadi M, Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn A, et al. GSK3 deficiencies in hematopoietic stem cells initiate pre-neoplastic state that is predictive of clinical outcomes of human acute leukemia. Cancer Cell. 2016;29:61–74.
Patel SA, Gerber JM. A user’s guide to novel therapies for acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2020;20:277–88.
Shafer D, Grant S. Update on rational targeted therapy in AML. Blood Rev. 2016;30:275–83.
Ruvolo PP, Qiu Y, Coombes KR, Zhang N, Neeley ES, Ruvolo VR, et al. Phosphorylation of GSK3α/β correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients. Biochim Biophys Acta-Clin. 2015;4:59–68.
Hou P, Wu C, Wang Y, Qi R, Bhavanasi D, Zuo Z, et al. A genome-wide CRISPR screen identifies genes critical for resistance to FLT3 inhibitor AC220. Cancer Res. 2017;77:4402–13.
Wang Z, Smith KS, Murphy M, Piloto O, Somervaille TC, Cleary ML. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature. 2008;455:1205–9.
Banerji V, Frumm SM, Ross KN, Li LS, Schinzel AC, Hahn CK, et al. The intersection of genetic and chemical genomic screens identifies GSK-3α as a target in human acute myeloid leukemia. J Clin Invest. 2012;122:935–47.
He L, Fei DL, Nagiec MJ, Mutvei AP, Lamprakis A, Kim BY, et al. Regulation of GSK3 cellular location by FRAT modulates mTORC1-dependent cell growth and sensitivity to rapamycin. Proc Natl Acad Sci USA. 2019;116:19523–9.
Pradere JP, Hernandez C, Koppe C, Friedman RA, Luedde T, Schwabe RF. Negative regulation of NF-κB p65 activity by serine 536 phosphorylation. Sci Signal. 2016;9:ra85.
Mishra M, Thacker G, Sharma A, Singh AK, Upadhyay V, Sanyal S, et al. FBW7 inhibits myeloid differentiation in acute myeloid leukemia via GSK3-dependent ubiquitination of PU.1. Mol Cancer Res. 2021;19:261–73.
Song EY, Palladinetti P, Klamer G, Ko KH, Lindeman R, O’Brien TA, et al. Glycogen synthase kinase-3β inhibitors suppress leukemia cell growth. Exp Hematol. 2010;38:908–21.
Hu S, Ueda M, Stetson L, Ignatz-Hoover J, Moreton S, Chakrabarti A, et al. A novel glycogen synthase kinase-3 inhibitor optimized for acute myeloid leukemia differentiation activity. Mol Cancer Ther. 2016;15:1485–94.
Gupta K, Stefan T, Ignatz-Hoover J, Moreton S, Parizher G, Saunthararajah Y, et al. GSK-3 inhibition sensitizes acute myeloid leukemia cells to 1,25D-mediated differentiation. Cancer Res. 2016;76:2743–53.
Takei H, Kobayashi SS. Targeting transcription factors in acute myeloid leukemia. Int J Hematol. 2019;109:28–34.
Antony-Debre I, Paul A, Leite J, Mitchell K, Kim HM, Carvajal LA, et al. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J Clin Invest. 2017;127:4297–313.
Rosenbauer F, Wagner K, Kutok JL, Iwasaki H, Le Beau MM, Okuno Y, et al. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet. 2004;36:624–30.
Pianigiani G, Betti C, Bigerna B, Rossi R, Brunetti L. PU.1 subcellular localization in acute myeloid leukaemia with mutated NPM1. Br J Haematol. 2020;188:184–7.
He L, Gomes AP, Wang X, Yoon SO, Lee G, Nagiec MJ, et al. mTORC1 promotes metabolic reprogramming by the suppression of GSK3-dependent Foxk1 phosphorylation. Mol Cell. 2018;70:949–60.
Lee YC, Shi YJ, Wang LJ, Chiou JT, Huang CH, Chang LS. GSK3β suppression inhibits MCL1 protein synthesis in human acute myeloid leukemia cells. J Cell Physiol. 2021;236:570–86.
Rizzieri DA, Cooley S, Odenike O, Moonan L, Chow KH, Jackson K, et al. An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia. Leuk Lymphoma. 2016;57:1800–6.
Thomas X. Acute promyelocytic leukemia: a history over 60 years-from the most malignant to the most curable form of acute leukemia. Oncol Ther. 2019;7:33–65.
Si J, Mueller L, Collins SJ. GSK3 inhibitors enhance retinoic acid receptor activity and induce the differentiation of retinoic acid-sensitive myeloid leukemia cells. Leukemia. 2011;25:1914–8.
Gupta K, Gulen F, Sun L, Aguilera R, Chakrabarti A, Kiselar J, et al. GSK3 is a regulator of RAR-mediated differentiation. Leukemia. 2012;26:1277–85.
Park S, Han HT, Oh SS, Kim DH, Jeong JW, Lee KW, et al. NDRG2 sensitizes myeloid leukemia to arsenic trioxide via GSK3β-NDRG2-PP2A complex formation. Cells. 2019;8:495.
Ueda M, Stefan T, Stetson L, Ignatz-Hoover JJ, Tomlinson B, Creger RJ, et al. Phase I trial of lithium and tretinoin for treatment of relapsed and refractory non-promyelocytic acute myeloid leukemia. Front Oncol. 2020;10:327.
Zassadowski F, Pokorna K, Ferre N, Guidez F, Llopis L, Chourbagi O, et al. Lithium chloride antileukemic activity in acute promyelocytic leukemia is GSK-3 and MEK/ERK dependent. Leukemia. 2015;29:2277–84.
Cancilla D, Rettig MP, DiPersio JF. Targeting CXCR4 in AML and ALL. Front Oncol. 2020;10:1672.
Hu K, Gu Y, Lou L, Liu L, Hu Y, Wang B, et al. Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway. J Hematol Oncol. 2015;8:1.
Takam Kamga P, Dal Collo G, Cassaro A, Bazzoni R, Delfino P, Adamo A, et al. Small molecule inhibitors of microenvironmental Wnt/β-catenin signaling enhance the chemosensitivity of acute myeloid leukemia. Cancers. 2020;12:2696.
Ruan Y, Kim HN, Ogana H, Kim YM. Wnt signaling in leukemia and its bone marrow microenvironment. Int J Mol Sci. 2020;21:6247.
Parameswaran R, Ramakrishnan P, Moreton SA, Xia Z, Hou Y, Lee DA, et al. Repression of GSK3 restores NK cell cytotoxicity in AML patients. Nat Commun. 2016;7:11154.
Graham JA, Fray M, de Haseth S, Lee KM, Lian MM, Chase CM, et al. Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition. J Biol Chem. 2010;285:32852–9.
Saleh R, Elkord E. FoxP3+ T regulatory cells in cancer: prognostic biomarkers and therapeutic targets. Cancer Lett. 2020;490:174–85.
Vadillo E, Dorantes-Acosta E, Pelayo R, Schnoor M. T cell acute lymphoblastic leukemia (T-ALL): new insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies. Blood Rev. 2018;32:36–51.
Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30:1663–9.
Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, et al. Improved survival for children and young adults with t-lineage acute lymphoblastic leukemia: results from the children’s oncology group AALL0434 methotrexate randomization. J Clin Oncol. 2018;36:2926–34.
Raetz EA, Teachey DT. T-cell acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program. 2016;2016:580–8.
Gokbuget N. How should we treat a patient with relapsed Ph-negative B-ALL and what novel approaches are being investigated? Best Pract Res Clin Haematol. 2017;30:261–74.
Zhou F, Zhang L, van Laar T, van Dam H, Ten Dijke P. GSK3β inactivation induces apoptosis of leukemia cells by repressing the function of c-Myb. Mol Biol Cell. 2011;22:3533–40.
Weathington NM, Snavely CA, Chen BB, Zhao J, Zhao Y, Mallampalli RK. Glycogen synthase kinase-3β stabilizes the interleukin (IL)-22 receptor from proteasomal degradation in murine lung epithelia. J Biol Chem. 2014;289:17610–9.
Wang XJ, Xu YH, Yang GC, Chen HX, Zhang P. Tetramethylpyrazine inhibits the proliferation of acute lymphocytic leukemia cell lines via decrease in GSK-3β. Oncol Rep. 2015;33:2368–74.
Tosello V, Bordin F, Yu J, Agnusdei V, Indraccolo S, Basso G, et al. Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation. Leukemia. 2016;30:812–2.
Lee JU, Kim LK, Choi JM. Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases. Front Immunol. 2018;9:2747.
Radadiya A, Zhu W, Coricello A, Alcaro S, Richards NGJ. Improving the treatment of acute lymphoblastic leukemia. Biochemistry. 2020;59:3193–200.
Lee JK, Kang S, Wang X, Rosales JL, Gao X, Byun HG, et al. HAP1 loss confers l-asparaginase resistance in ALL by downregulating the calpain-1-Bid-caspase-3/12 pathway. Blood. 2019;133:2222–32.
Hinze L, Pfirrmann M, Karim S, Degar J, McGuckin C, Vinjamur D, et al. Synthetic lethality of Wnt pathway activation and asparaginase in drug-resistant acute leukemias. Cancer Cell. 2019;35:664–76.
Chiarini F, Paganelli F, Martelli AM, Evangelisti C. The role played by Wnt/β-catenin signaling pathway in acute lymphoblastic leukemia. Int J Mol Sci. 2020;21:1098.
Evangelisti C, Chiarini F, Cappellini A, Paganelli F, Fini M, Santi S, et al. Targeting Wnt/β-catenin and PI3K/Akt/mTOR pathways in T-cell acute lymphoblastic leukemia. J Cell Physiol. 2020;235:5413–28.
Borga C, Foster CA, Iyer S, Garcia SP, Langenau DM, Frazer JK. Molecularly distinct models of zebrafish Myc-induced B cell leukemia. Leukemia. 2019;33:559–62.
Galluzzi L, Spranger S, Fuchs E, Lopez-Soto A. WNT signaling in cancer immunosurveillance. Trends Cell Biol. 2019;29:44–65.
Nomura S, Takahashi H, Suzuki J, Kuwahara M, Yamashita M, Sawasaki T. Pyrrothiogatain acts as an inhibitor of GATA family proteins and inhibits Th2 cell differentiation in vitro. Sci Rep. 2019;9:17335.
Martin-Acosta P, Xiao X. PROTACs to address the challenges facing small molecule inhibitors. Eur J Med Chem. 2021;210:112993.
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Martelli, A.M., Evangelisti, C., Paganelli, F. et al. GSK-3: a multifaceted player in acute leukemias. Leukemia (2021). https://doi.org/10.1038/s41375-021-01243-z