Recurrent Missense Driver STAT5B N642H Mutation in Children Transiting into Adolescence, with Acute Lymphoid Leukemia and its In silico Inhibition


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Background:The occurrence of gain of function mutations in STAT5B has been associated to survival, and drug resistance in Leukemia. In silico screening of compounds having inhibitory potential towards mutated proteins, can be helpful in the development of specific inhibitors.

Objective:This study was designed to screen selected JAK-STAT mutations in leukemia patients and virtual exploration of molecular interaction of potential inhibitors with their mutated products.

Methods:In total 276 patients were randomly recruited for this study. Demographic and clinical data were summarized. The genetic status of JAK1V623A, JAK2 S473 and STAT5BN642H were screened through allele specific PCR. In-silico analysis was performed on wild type and mutant protein sequences retrieved from Protein databank. The ligands and protein were prepared through standard protocols, and docking was performed through Auto Dock Vina 1.2.0.

Results:Acute lymphoblastic leukemia comprises 70% of the total patients. Male to female ratio was 3:1. All the patients were homozygous for JAK1V623A, JAK2 S473 major allele. However, 6 patients (5 male, 1 female) with ALL were STAT5BN642H+. The molecular docking of the ligands to wild type and STAT5BN642H+revealed that AC- 4-130, Pimozide, Indirubin and Stafib-2 have higher but differential docking affinities for SH2-domain of both normal and mutated STAT5B. However, AC-4-130 has a higher affinity for wild type and Stafib-2 has stable molecular interaction with STAT5BN642H+.

Conclusion:The aggressive form of pediatric leukemia, carrying STAT5BN642H+ mutation is identified in the studied population. It is predicted that AC-14-30 and stafib-2 have potential for inhibition of constitutively active STAT5B if optimized for use in combination therapy.

Об авторах

Rehana Yasmin

, Institute of Biomedical and Genetic Engineering

Email: info@benthamscience.net

Rashda Abbasi

, Institute of Biomedical and Genetic Engineering

Автор, ответственный за переписку.
Email: info@benthamscience.net

Tajdar Gohar

Department of Pharmacy, COMSATS University

Email: info@benthamscience.net

Hina

Sarhad Institute of Allied Health Sciences, Faculty of Life Sciences, Sarhad University of Science and Technology

Email: info@benthamscience.net

Nafees Ahmad

, Institute of Biomedical and Genetic Engineering

Email: info@benthamscience.net

Sajid Malik

Human Genetics Program, Department of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Maurer, B.; Kollmann, S.; Pickem, J.; Hoelbl-Kovacic, A.; Sexl, V. STAT5A and STAT5B—twins with different personalities in hematopoiesis and leukemia. Cancers (Basel), 2019, 11(11), 1726. doi: 10.3390/cancers11111726 PMID: 31690038
  2. Hammarén, H.M.; Virtanen, A.T.; Raivola, J.; Silvennoinen, O. The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine, 2019, 118, 48-63. doi: 10.1016/j.cyto.2018.03.041 PMID: 29685781
  3. Villarino, A.V.; Kanno, Y.; O’Shea, J.J. Mechanisms and consequences of Jak–STAT signaling in the immune system. Nat. Immunol., 2017, 18(4), 374-384. doi: 10.1038/ni.3691 PMID: 28323260
  4. Waldmann, T.A.; Chen, J. Disorders of the JAK/STAT pathway in T cell lymphoma pathogenesis: Implications for immunotherapy. Annu. Rev. Immunol., 2017, 35(1), 533-550. doi: 10.1146/annurev-immunol-110416-120628 PMID: 28182501
  5. Murray, P.J. The JAK-STAT signaling pathway: input and output integration. J. Immunol., 2007, 178(5), 2623-2629. doi: 10.4049/jimmunol.178.5.2623 PMID: 17312100
  6. Owen, K.L.; Brockwell, N.K.; Parker, B.S. JAK-STAT signaling: A double-edged sword of immune regulation and cancer progression. Cancers (Basel), 2019, 11(12), 2002. doi: 10.3390/cancers11122002 PMID: 31842362
  7. Matutes, E. The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms. Int. J. Lab. Hematol., 2018, 40(S1)(Suppl. 1), 97-103. doi: 10.1111/ijlh.12817 PMID: 29741263
  8. Shahmarvand, N.; Nagy, A.; Shahryari, J.; Ohgami, R.S. Mutations in the signal transducer and activator of transcription family of genes in cancer. Cancer Sci., 2018, 109(4), 926-933. doi: 10.1111/cas.13525 PMID: 29417693
  9. de Araujo, E.D.; Orlova, A.; Neubauer, H.A.; Bajusz, D.; Seo, H.S.; Dhe-Paganon, S.; Keserű, G.M.; Moriggl, R.; Gunning, P.T. Structural implications of STAT3 and STAT5 SH2 domain mutations. Cancers (Basel), 2019, 11(11), 1757. doi: 10.3390/cancers11111757 PMID: 31717342
  10. de Araujo, E.D.; Erdogan, F.; Neubauer, H.A.; Meneksedag-Erol, D.; Manaswiyoungkul, P.; Eram, M.S.; Seo, H.S.; Qadree, A.K.; Israelian, J.; Orlova, A.; Suske, T.; Pham, H.T.T.; Boersma, A.; Tangermann, S.; Kenner, L.; Rülicke, T.; Dong, A.; Ravichandran, M.; Brown, P.J.; Audette, G.F.; Rauscher, S.; Dhe-Paganon, S.; Moriggl, R.; Gunning, P.T. Structural and functional consequences of the STAT5BN642H driver mutation. Nat. Commun., 2019, 10(1), 2517. doi: 10.1038/s41467-019-10422-7 PMID: 31175292
  11. Halim, C.E.; Deng, S.; Ong, M.S.; Yap, C.T. Involvement of STAT5 in oncogenesis. Biomedicines, 2020, 8(9), 316. doi: 10.3390/biomedicines8090316 PMID: 32872372
  12. Wan, P.; He, X.; Han, Y.; Wang, L.; Yuan, Z. Stat5 inhibits NLRP3 -mediated pyroptosis to enhance chemoresistance of breast cancer cells via promoting MIR -182 transcription. Chem. Biol. Drug Des., 2023, 102(1), 14-25. doi: 10.1111/cbdd.14229 PMID: 36905318
  13. Bhattacharya, D.; Teramo, A.; Gasparini, V.R.; Huuhtanen, J.; Kim, D.; Theodoropoulos, J.; Schiavoni, G.; Barilà, G.; Vicenzetto, C.; Calabretto, G.; Facco, M.; Kawakami, T.; Nakazawa, H.; Falini, B.; Tiacci, E.; Ishida, F.; Semenzato, G.; Kelkka, T.; Zambello, R.; Mustjoki, S. Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia. Blood Cancer J., 2022, 12(2), 31. doi: 10.1038/s41408-022-00630-8 PMID: 35210405
  14. Raj, S.; Sasidharan, S.; Dubey, V.K.; Saudagar, P. Identification of lead molecules against potential drug target protein MAPK4 from L. donovani: An in-silico approach using docking, molecular dynamics and binding free energy calculation. PLoS One, 2019, 14(8), e0221331. doi: 10.1371/journal.pone.0221331 PMID: 31425543
  15. Hughes, J.P.; Rees, S.; Kalindjian, S.B.; Philpott, K.L. Principles of early drug discovery. Br. J. Pharmacol., 2011, 162(6), 1239-1249. doi: 10.1111/j.1476-5381.2010.01127.x PMID: 21091654
  16. Chen, D.; Oezguen, N.; Urvil, P.; Ferguson, C.; Dann, S.M.; Savidge, T.C. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci. Adv., 2016, 2(3), e1501240. doi: 10.1126/sciadv.1501240 PMID: 27051863
  17. Kumar, Y.; Singh, H.; Patel, C.N. In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing. J. Infect. Public Health, 2020, 13(9), 1210-1223. doi: 10.1016/j.jiph.2020.06.016 PMID: 32561274
  18. Hall, D.C., Jr; Ji, H.F. A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Med. Infect. Dis., 2020, 35, 101646. doi: 10.1016/j.tmaid.2020.101646 PMID: 32294562
  19. Rahman, F.; Tabrez, S.; Ali, R.; Alqahtani, A.S.; Ahmed, M.Z.; Rub, A. Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins. J. Tradit. Complement. Med., 2021, 11(2), 173-179. doi: 10.1016/j.jtcme.2021.01.006 PMID: 33520682
  20. Alnajjar, R.; Mostafa, A.; Kandeil, A.; Al-Karmalawy, A.A. Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease. Heliyon, 2020, 6(12), e05641. doi: 10.1016/j.heliyon.2020.e05641 PMID: 33294721
  21. Bhattacharya, K.; Bordoloi, R.; Chanu, N.R.; Kalita, R.; Sahariah, B.J.; Bhattacharjee, A. In silico discovery of 3 novel quercetin derivatives against papain-like protease, spike protein, and 3C-like protease of SARS-CoV-2. J. Genet. Eng. Biotechnol., 2022, 20(1), 43. doi: 10.1186/s43141-022-00314-7 PMID: 35262828
  22. Parks, J.; Smith, J. Clinical implications of basic research how to discover., 2020, 1-4.
  23. Pham, H.T.T.; Maurer, B.; Prchal-Murphy, M.; Grausenburger, R.; Grundschober, E.; Javaheri, T.; Nivarthi, H.; Boersma, A.; Kolbe, T.; Elabd, M.; Halbritter, F.; Pencik, J.; Kazemi, Z.; Grebien, F.; Hengstschläger, M.; Kenner, L.; Kubicek, S.; Farlik, M.; Bock, C.; Valent, P.; Müller, M.; Rülicke, T.; Sexl, V.; Moriggl, R. STAT5BN642H is a driver mutation for T cell neoplasia. J. Clin. Invest., 2017, 128(1), 387-401. doi: 10.1172/JCI94509 PMID: 29200404
  24. Diop, A.; Santorelli, D.; Malagrinò, F.; Nardella, C.; Pennacchietti, V.; Pagano, L.; Marcocci, L.; Pietrangeli, P.; Gianni, S.; Toto, A. SH2 domains: folding, binding and therapeutical approaches. Int. J. Mol. Sci., 2022, 23(24), 15944. doi: 10.3390/ijms232415944 PMID: 36555586
  25. Keilhack, H.; David, F.S.; McGregor, M.; Cantley, L.C.; Neel, B.G. Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. J. Biol. Chem., 2005, 280(35), 30984-30993. doi: 10.1074/jbc.M504699200 PMID: 15987685
  26. Niihori, T.; Aoki, Y.; Ohashi, H.; Kurosawa, K.; Kondoh, T.; Ishikiriyama, S.; Kawame, H.; Kamasaki, H.; Yamanaka, T.; Takada, F.; Nishio, K.; Sakurai, M.; Tamai, H.; Nagashima, T.; Suzuki, Y.; Kure, S.; Fujii, K.; Imaizumi, M.; Matsubara, Y. Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia. J. Hum. Genet., 2005, 50(4), 192-202. doi: 10.1007/s10038-005-0239-7 PMID: 15834506
  27. Bandapalli, O.R.; Schuessele, S.; Kunz, J.B.; Rausch, T.; Stütz, A.M.; Tal, N.; Geron, I.; Gershman, N.; Izraeli, S.; Eilers, J. The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse. Haematologica, 2014, 99(10), e188.
  28. Kiel, M.J.; Velusamy, T.; Rolland, D.; Sahasrabuddhe, A.A.; Chung, F.; Bailey, N.G.; Schrader, A.; Li, B.; Li, J.Z.; Ozel, A.B.; Betz, B.L.; Miranda, R.N.; Medeiros, L.J.; Zhao, L.; Herling, M.; Lim, M.S.; Elenitoba-Johnson, K.S.J. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood, 2014, 124(9), 1460-1472. doi: 10.1182/blood-2014-03-559542 PMID: 24825865
  29. Ma, X.; Wen, L.; Wu, L.; Wang, Q.; Yao, H.; Wang, Q.; Ma, L.; Chen, S. Rare occurrence of a STAT5B N642H mutation in adult T-cell acute lymphoblastic leukemia. Cancer Genet., 2015, 208(1-2), 52-53. doi: 10.1016/j.cancergen.2014.12.001 PMID: 25749351
  30. Rajala, H.L.M.; Eldfors, S.; Kuusanmäki, H.; van Adrichem, A.J.; Olson, T.; Lagström, S.; Andersson, E.I.; Jerez, A.; Clemente, M.J.; Yan, Y.; Zhang, D.; Awwad, A.; Ellonen, P.; Kallioniemi, O.; Wennerberg, K.; Porkka, K.; Maciejewski, J.P.; Loughran, T.P., Jr; Heckman, C.; Mustjoki, S. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, 2013, 121(22), 4541-4550. doi: 10.1182/blood-2012-12-474577 PMID: 23596048
  31. Rajala, H.L.M.; Porkka, K.; Maciejewski, J.P.; Loughran, T.P., Jr; Mustjoki, S. Uncovering the pathogenesis of large granular lymphocytic leukemia—novel STAT3 and STAT5b mutations. Ann. Med., 2014, 46(3), 114-122. doi: 10.3109/07853890.2014.882105 PMID: 24512550
  32. Luo, Q.; Shen, J.; Yang, Y.; Tang, H.; Shi, M.; Liu, J.; Liu, Z.; Shi, X.; Yi, Y. CSF3R T618I, ASXL1 G942 fs and STAT5B N642H trimutation co-contribute to a rare chronic neutrophilic leukaemia manifested by rapidly progressive leucocytosis, severe infections, persistent fever and deep venous thrombosis. Br. J. Haematol., 2018, 180(6), 892-894. doi: 10.1111/bjh.14456 PMID: 27984641
  33. Cross, N.C.P.; Hoade, Y.; Tapper, W.J.; Carreno-Tarragona, G.; Fanelli, T.; Jawhar, M.; Naumann, N.; Pieniak, I.; Lübke, J.; Ali, S.; Bhuller, K.; Burgstaller, S.; Cargo, C.; Cavenagh, J.; Duncombe, A.S.; Das-Gupta, E.; Evans, P.; Forsyth, P.; George, P.; Grimley, C.; Jack, F.; Munro, L.; Mehra, V.; Patel, K.; Rismani, A.; Sciuccati, G.; Thomas-Dewing, R.; Thornton, P.; Virchis, A.; Watt, S.; Wallis, L.; Whiteway, A.; Zegocki, K.; Bain, B.J.; Reiter, A.; Chase, A. Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia. Leukemia, 2019, 33(2), 415-425. doi: 10.1038/s41375-018-0342-3 PMID: 30573779
  34. Babushok, D.V.; Perdigones, N.; Perin, J.C.; Olson, T.S.; Ye, W.; Roth, J.J.; Lind, C.; Cattier, C.; Li, Y.; Hartung, H.; Paessler, M.E.; Frank, D.M.; Xie, H.M.; Cross, S.; Cockroft, J.D.; Podsakoff, G.M.; Monos, D.; Biegel, J.A.; Mason, P.J.; Bessler, M. Emergence of clonal hematopoiesis in the majority of patients with acquired aplastic anemia. Cancer Genet., 2015, 208(4), 115-128. doi: 10.1016/j.cancergen.2015.01.007 PMID: 25800665
  35. Hennighausen, L.; Robinson, G.W. Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev., 2008, 22(6), 711-721. doi: 10.1101/gad.1643908 PMID: 18347089
  36. Nelson, E.A.; Walker, S.R.; Xiang, M.; Weisberg, E.; Bar-Natan, M.; Barrett, R.; Liu, S.; Kharbanda, S.; Christie, A.L.; Nicolais, M.; Griffin, J.D.; Stone, R.M.; Kung, A.L.; Frank, D.A. The STAT5 inhibitor pimozide displays efficacy in models of acute myelogenous leukemia driven by FLT3 mutations. Genes Cancer, 2012, 3(7-8), 503-511. doi: 10.1177/1947601912466555 PMID: 23264850
  37. Nam, S.; Scuto, A.; Yang, F.; Chen, W.; Park, S.; Yoo, H.S.; Konig, H.; Bhatia, R.; Cheng, X.; Merz, K.H.; Eisenbrand, G.; Jove, R. Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling. Mol. Oncol., 2012, 6(3), 276-283. doi: 10.1016/j.molonc.2012.02.002 PMID: 22387217
  38. World Health Organization. Regional Office for the Eastern Mediterranean. ( 2019) . Healthy diet. World Health Organization. Regional Office for the Eastern Mediterranean. 2019. Available from: https://iris.who.int/handle/10665/325828 (accessed on 12-11-2024).
  39. Miller, S.A.; Dykes, D.D.; Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., 1988, 16(3), 1215. doi: 10.1093/nar/16.3.1215 PMID: 3344216
  40. Brachet-Botineau, M.; Deynoux, M.; Vallet, N.; Polomski, M.; Juen, L.; Hérault, O.; Mazurier, F.; Viaud-Massuard, M.C.; Prié, G.; Gouilleux, F. A novel inhibitor of STAT5 signaling overcomes chemotherapy resistance in myeloid leukemia cells. Cancers (Basel), 2019, 11(12), 2043. doi: 10.3390/cancers11122043 PMID: 31861239
  41. Cumaraswamy, A.A.; Lewis, A.M.; Geletu, M.; Todic, A.; Diaz, D.B.; Cheng, X.R.; Brown, C.E.; Laister, R.C.; Muench, D.; Kerman, K.; Grimes, H.L.; Minden, M.D.; Gunning, P.T. Nanomolar-potency small molecule inhibitor of STAT5 Protein. ACS Med. Chem. Lett., 2014, 5(11), 1202-1206. doi: 10.1021/ml500165r PMID: 25419444
  42. Wingelhofer, B.; Maurer, B.; Heyes, E.C.; Cumaraswamy, A.A.; Berger-Becvar, A.; de Araujo, E.D.; Orlova, A.; Freund, P.; Ruge, F.; Park, J.; Tin, G.; Ahmar, S.; Lardeau, C.H.; Sadovnik, I.; Bajusz, D.; Keserű, G.M.; Grebien, F.; Kubicek, S.; Valent, P.; Gunning, P.T.; Moriggl, R. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia, 2018, 32(5), 1135-1146. doi: 10.1038/s41375-017-0005-9 PMID: 29472718
  43. Su, L.; David, M. Distinct mechanisms of STAT phosphorylation via the interferon-alpha/beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J. Biol. Chem., 2000, 275(17), 12661-12666. doi: 10.1074/jbc.275.17.12661 PMID: 10777558
  44. Mistry, H.; Hsieh, G.; Buhrlage, S.J.; Huang, M.; Park, E.; Cuny, G.D.; Galinsky, I.; Stone, R.M.; Gray, N.S.; D’Andrea, A.D.; Parmar, K. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol. Cancer Ther., 2013, 12(12), 2651-2662. doi: 10.1158/1535-7163.MCT-13-0103-T PMID: 24130053
  45. Elumalai, N.; Berg, A.; Rubner, S.; Blechschmidt, L.; Song, C.; Natarajan, K.; Matysik, J.; Berg, T. Rational development of Stafib-2: a selective, nanomolar inhibitor of the transcription factor STAT5b. Sci. Rep., 2017, 7(1), 819. doi: 10.1038/s41598-017-00920-3 PMID: 28400581
  46. Pinz, S.; Unser, S.; Rascle, A. The natural chemopreventive agent sulforaphane inhibits STAT5 activity. PLoS One, 2014, 9(6), e99391. doi: 10.1371/journal.pone.0099391 PMID: 24910998
  47. BIOVIA Discovery Studio. 2021. Available from: https://www.3ds.com/products/biovia/discovery-studio (accessed on 12-11-2024).
  48. Eberhardt, J.; Santos-Martins, D.; Tillack, A.F.; Forli, S. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model., 2021, 61(8), 3891-3898. doi: 10.1021/acs.jcim.1c00203 PMID: 34278794
  49. Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612. doi: 10.1093/nar/gkaa1074 PMID: 33237311
  50. Kavesh, M.; Mohebnasab, M.; Angel, M.R.; Xie, W.; Raess, P.W.; Cui, W.; Press, R.D.; Yang, G.; Li, P. Distinguishing STAT3/STAT5B -mutated large granular lymphocyte leukemia from myeloid neoplasms by genetic profiling. Blood Adv., 2023, 7(1), 40-45. doi: 10.1182/bloodadvances.2022008192 PMID: 35939786
  51. Qu, S.; Jia, Y.; Wang, H.; Ai, X.; Xu, Z.; Qin, T.; Pan, L.; Li, B.; Huang, G.; Gale, R.P.; Xiao, Z. STAT3 and STAT5B mutations have unique distribution in T-cell large granular lymphocyte proliferations and advanced myeloid neoplasms. Leuk. Lymphoma, 2021, 62(6), 1506-1509. doi: 10.1080/10428194.2020.1869964 PMID: 33410350
  52. Andersson, E.I.; Tanahashi, T.; Sekiguchi, N.; Gasparini, V.R.; Bortoluzzi, S.; Kawakami, T.; Matsuda, K.; Mitsui, T.; Eldfors, S.; Bortoluzzi, S.; Coppe, A.; Binatti, A.; Lagström, S.; Ellonen, P.; Fukushima, N.; Nishina, S.; Senoo, N.; Sakai, H.; Nakazawa, H.; Kwong, Y.L.; Loughran, T.P.; Maciejewski, J.P.; Mustjoki, S.; Ishida, F. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. Blood, 2016, 128(20), 2465-2468. doi: 10.1182/blood-2016-06-724856 PMID: 27697773
  53. Umrau, K.; Naganuma, K.; Gao, Q.; Dogan, A.; Kizaki, M.; Roshal, M.; Liu, Y.; Yabe, M. Activating STAT5B mutations can cause both primary hypereosinophilia and lymphocyte-variant hypereosinophilia. Leuk. Lymphoma, 2023, 64(1), 238-241. doi: 10.1080/10428194.2022.2131413 PMID: 36308018
  54. Bourgeais, J.; Ishac, N.; Medrzycki, M.; Brachet-Botineau, M.; Desbourdes, L.; Gouilleux-Gruart, V.; Pecnard, E.; Rouleux-Bonnin, F.; Gyan, E.; Domenech, J.; Mazurier, F.; Moriggl, R.; Bunting, K.D.; Herault, O.; Gouilleux, F. Oncogenic STAT5 signaling promotes oxidative stress in chronic myeloid leukemia cells by repressing antioxidant defenses. Oncotarget, 2017, 8(26), 41876-41889. doi: 10.18632/oncotarget.11480 PMID: 27566554
  55. Hu, Z.; Medeiros, L.J.; Xu, M.; Yuan, J.; Peker, D.; Shao, L.; Tang, Z.; Mai, B.; Thakral, B.; Rios, A.; Hu, S.; Wang, W. T-cell prolymphocytic leukemia with t(X;14)(q28;q11.2): A clinicopathologic study of 15 cases. Am. J. Clin. Pathol., 2023, 159(4), 325-336. doi: 10.1093/ajcp/aqac166 PMID: 36883805
  56. Suske, T.; Sorger, H.; Manhart, G.; Ruge, F.; Prutsch, N.; Zimmerman, M.W.; Eder, T.; Abdallah, D.I.; Maurer, B.; Wagner, C.; Schönefeldt, S.; Spirk, K.; Pichler, A.; Pemovska, T.; Schweicker, C.; Pölöske, D.; Hubanic, E.; Jungherz, D.; Müller, T.A.; Aung, M.M.K.; Orlova, A.; Pham, H.T.T.; Zimmel, K.; Krausgruber, T.; Bock, C.; Müller, M.; Dahlhoff, M.; Boersma, A.; Rülicke, T.; Fleck, R.; de Araujo, E.D.; Gunning, P.T.; Aittokallio, T.; Mustjoki, S.; Sanda, T.; Hartmann, S.; Grebien, F.; Hoermann, G.; Haferlach, T.; Staber, P.B.; Neubauer, H.A.; Look, A.T.; Herling, M.; Moriggl, R. Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia. J. Clin. Invest., 2024, 134(8), e168536. doi: 10.1172/JCI168536 PMID: 38618957
  57. Neubauer, H.A.; Suske, T.; Schönefeldt, S.; Tangermann, S.; Boersma, A.; Rülicke, T.; Bekiaris, V.; Kenner, L.; Moriggl, R. Abstract 2752: The gain-of-function STAT5BN642H mutation as a driver of mature T cell leukemia/lymphoma. Cancer Res., 2020, 80(16)(Suppl.), 2752-2752. doi: 10.1158/1538-7445.AM2020-2752
  58. Ullah, F.; Markouli, M.; Orland, M.; Ogbue, O.; Dima, D.; Omar, N.; Mustafa Ali, M.K. Large granular lymphocytic leukemia: Clinical features, molecular pathogenesis, diagnosis and treatment. Cancers (Basel), 2024, 16(7), 1307. doi: 10.3390/cancers16071307 PMID: 38610985
  59. Klein, K.; Kollmann, S.; Hiesinger, A.; List, J.; Kendler, J.; Klampfl, T.; Rhandawa, M.; Trifinopoulos, J.; Maurer, B.; Grausenburger, R.; Betram, C.A.; Moriggl, R.; Rülicke, T.; Mullighan, C.G.; Witalisz-Siepracka, A.; Walter, W.; Hoermann, G.; Sexl, V.; Gotthardt, D. A lineage-specific STAT5B N642H mouse model to study NK-cell leukemia. Blood, 2024, 143(24), 2474-2489. doi: 10.1182/blood.2023022655 PMID: 38498036
  60. Yin, C.C.; Tam, W.; Walker, S.M.; Kaur, A.; Ouseph, M.M.; Xie, W.; Weinberg, K. O.; Li, P.; Zuo, Z.; Routbort, M.J.; Chen, S.; Medeiros, L.J.; George, T.I.; Orazi, A.; Arber, D.A.; Bagg, A.; Hasserjian, R.P.; Wang, S.A. STAT5B mutations in myeloid neoplasms differ by disease subtypes but characterize a subset of chronic myeloid neoplasms with eosinophilia and/or basophilia. Haematologica, 2024, 109(6), 1825-1835. PMID: 37981812
  61. Ullah, S.; Tonks, A.; A Halawi, M. A M, A.; Alkuwaykibi, M.; Halawi, A.; Hayat, A.; Alkoumi, H.A.H.; Alanzi, M.; Wadood, A. Whole exome sequence of Pakistani acute lymphocytic leukemia patient from Pakhtuns ancestry reveal the novel genetic variant characterization in the GLDC gene. J. Biotechnol. Biomed., 2023, 6(3), 409-420. doi: 10.26502/jbb.2642-91280103
  62. Ahmed, Z.A.; Nasir, A.; Sheikh, M.S.; Rizvi, A.Q.; Moatter, T. Characteristics of BCR-ABL rearrangement variants in Pakistani patients with chronic myeloid leukemia and acute lymphocytic leukemia. Ann. Oncol., 2019, 30, ix94. doi: 10.1093/annonc/mdz427.011
  63. Shahid, S.; Shakeel, M.; Siddiqui, S.; Ahmed, S.; Sohail, M.; Khan, I.A.; Abid, A.; Shamsi, T. Novel genetic variations in acute myeloid leukemia in Pakistani population. Front. Genet., 2020, 11, 560. doi: 10.3389/fgene.2020.00560 PMID: 32655615
  64. Shabih, H.; Mahmood, A. AKhtar, F.; Mahmood, R.; Muzafar, S.; Batool, M. BCR-ABL1 Gene mutation in acute lymphoblastic leukemia. Annal. PIMS-Shaheed Zulfiqar Ali Bhutto Med. Uni., 2022, 18(3), 181-185. doi: 10.48036/apims.v18i3.629
  65. Azad, A.K.; Khan, M.R.; Habib, A.B.M.H.; Miah, M.A.W.; Begum, M. Aberrant expression of CD markers in acute myeloid leukaemia. Haematol. J. Bangladesh, 2020, 2(1), 14-16. doi: 10.37545/haematoljbd201812
  66. Faiz, M.; Azeem, M.; Qureshi, A. Incidence of flt3-itd gene mutations among Pakistani patients with acute lymphoblastic leukemia patients: A preliminary study. Int. J. Med. Lab Res., 2018, 3(2), 1-6.
  67. Corsello, S.M.; Bittker, J.A.; Liu, Z.; Gould, J.; McCarren, P.; Hirschman, J.E.; Johnston, S.E.; Vrcic, A.; Wong, B.; Khan, M.; Asiedu, J.; Narayan, R.; Mader, C.C.; Subramanian, A.; Golub, T.R. The Drug Repurposing Hub: A next-generation drug library and information resource. Nat. Med., 2017, 23(4), 405-408. doi: 10.1038/nm.4306 PMID: 28388612
  68. Ghanem, A.; Emara, H.A.; Muawia, S.; Abd El Maksoud, A.I.; Al-Karmalawy, A.A.; Elshal, M.F. Tanshinone IIA synergistically enhances the antitumor activity of doxorubicin by interfering with the PI3K/AKT/mTOR pathway and inhibition of topoisomerase II: in vitro and molecular docking studies. New J. Chem., 2020, 44(40), 17374-17381. doi: 10.1039/D0NJ04088F
  69. Eliaa, S.G.; Al-Karmalawy, A.A.; Saleh, R.M.; Elshal, M.F. Empagliflozin and doxorubicin synergistically inhibit the survival of triple-negative breast cancer cells via interfering with the mtor pathway and inhibition of calmodulin: In vitro and molecular docking studies. ACS Pharmacol. Transl. Sci., 2020, 3(6), 1330-1338. doi: 10.1021/acsptsci.0c00144 PMID: 33344906
  70. Barrows, N.; Campos, R.; Powell, S.; Prasanth, K.; Schott-Lerner, G.; Soto-Acosta, R. A screen of FDA-approved drugs for inhibitors of zika virus infection. Cell Host Microbe, 2016, 20(2), 259-270.
  71. Tremblay, C.S.; Saw, J.; Boyle, J.A.; Haigh, K.; Litalien, V.; McCalmont, H.R.; Evans, K.; Lock, R.B.; Jane, S.M.; Haigh, J.J.; Curtis, D.J. STAT5 activation promotes progression and chemotherapy- resistance in early T-cell precursor acute lymphoblastic leukemia. Blood, 2023, 142(3), blood.2022016322. doi: 10.1182/blood.2022016322 PMID: 369894892
  72. Nelson, E.A.; Walker, S.R.; Weisberg, E.; Bar-Natan, M.; Barrett, R.; Gashin, L.B.; Terrell, S.; Klitgaard, J.L.; Santo, L.; Addorio, M.R.; Ebert, B.L.; Griffin, J.D.; Frank, D.A. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood, 2011, 117(12), 3421-3429. doi: 10.1182/blood-2009-11-255232 PMID: 21233313
  73. Walker, S.R.; Xiang, M.; Frank, D.A. Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer. Mol. Cell. Endocrinol., 2014, 382(1), 616-621. doi: 10.1016/j.mce.2013.03.010 PMID: 23531638
  74. Simpson, H.M.; Furusawa, A.; Sadashivaiah, K.; Civin, C.I.; Banerjee, A. STAT5 inhibition induces TRAIL/DR4 dependent apoptosis in peripheral T-cell lymphoma. Oncotarget, 2018, 9(24), 16792-16806. doi: 10.18632/oncotarget.24698 PMID: 29682185

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