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Gene Mutations and Targeted Therapies of Myeloid Sarcoma

  • Leukemia (PH Wiernik, Section Editor)
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Opinion statement

Myeloid sarcoma, a rare malignant tumor characterized by the invasion of extramedullary tissue by immature myeloid cells, commonly occurs concomitantly with acute myeloid leukemia, myelodysplastic syndromes, or myeloproliferative neoplasms. The rarity of myeloid sarcoma poses challenges for diagnosis and treatment. Currently, treatments for myeloid sarcoma remain controversial and primarily follow protocols for acute myeloid leukemia, such as chemotherapy utilizing multi-agent regimens, in addition to radiation therapy and/or surgery. The advancements in next-generation sequencing technology have led to significant progress in the field of molecular genetics, resulting in the identification of both diagnostic and therapeutic targets. The application of targeted therapeutics, such as FMS-like tyrosine kinase 3(FLT3) inhibitors, isocitrate dehydrogenases(IDH) inhibitors, and the B cell lymphoma 2(BCL2) inhibitors, has facilitated the gradual transformation of traditional chemotherapy into targeted precision therapy for acute myeloid leukemia. However, the field of targeted therapy for myeloid sarcoma is relatively under-investigated and not well-described. In this review, we comprehensively summarize the molecular genetic characteristics of myeloid sarcoma and the current application of targeted therapeutics.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703–19. https://doi.org/10.1038/s41375-022-01613-1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Solh M, Solomon S, Morris L, Holland K, Bashey A. Extramedullary acute myelogenous leukemia. Blood Rev. 2016;30(5):333–9. https://doi.org/10.1016/j.blre.2016.04.001.

    Article  PubMed  Google Scholar 

  3. Shahin OA, Ravandi F. Myeloid sarcoma. Curr Opin Hematol. 2020;27(2):88–94. https://doi.org/10.1097/MOH.0000000000000571.

    Article  CAS  PubMed  Google Scholar 

  4. Eckardt JN, Stolzel F, Kunadt D, Rollig C, Stasik S, Wagenfuhr L, et al. Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. J Hematol Oncol. 2022;15(1):60. https://doi.org/10.1186/s13045-022-01267-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Claerhout H, Van Aelst S, Melis C, Tousseyn T, Gheysens O, Vandenberghe P, et al. Clinicopathological characteristics of de novo and secondary myeloid sarcoma: a monocentric retrospective study. Eur J Haematol. 2018;100(6):603–12. https://doi.org/10.1111/ejh.13056.

    Article  CAS  PubMed  Google Scholar 

  6. Stolzel F, Luer T, Lock S, Parmentier S, Kuithan F, Kramer M, et al. The prevalence of extramedullary acute myeloid leukemia detected by (18)FDG-PET/CT: final results from the prospective PETAML trial. Haematologica. 2020;105(6):1552–8. https://doi.org/10.3324/haematol.2019.223032.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Shimizu H, Saitoh T, Hatsumi N, Takada S, Handa H, Jimbo T, et al. Prevalence of extramedullary relapses is higher after allogeneic stem cell transplantation than after chemotherapy in adult patients with acute myeloid leukemia. Leuk Res. 2013;37(11):1477–81. https://doi.org/10.1016/j.leukres.2013.08.017.

    Article  CAS  PubMed  Google Scholar 

  8. Dohner H, Wei AH, Lowenberg B. Towards precision medicine for AML. Nat Rev Clin Oncol. 2021;18(9):577–90. https://doi.org/10.1038/s41571-021-00509-w.

    Article  PubMed  Google Scholar 

  9. Shallis RM, Gale RP, Lazarus HM, Roberts KB, Xu ML, Seropian SE, et al. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved. Blood Rev. 2021;47:100773. https://doi.org/10.1016/j.blre.2020.100773.

    Article  CAS  PubMed  Google Scholar 

  10. Kaur V, Swami A, Alapat D, Abdallah AO, Motwani P, Hutchins LF, et al. Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years. Hematology. 2018;23(1):17–24. https://doi.org/10.1080/10245332.2017.1333275.

    Article  CAS  PubMed  Google Scholar 

  11. Almond LM, Charalampakis M, Ford SJ, Gourevitch D, Desai A. Myeloid sarcoma: presentation, diagnosis, and treatment. Clin Lymphoma Myeloma Leuk. 2017;17(5):263–7. https://doi.org/10.1016/j.clml.2017.02.027.

    Article  PubMed  Google Scholar 

  12. Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21(2):340–50. https://doi.org/10.1038/sj.leu.2404491.

    Article  CAS  PubMed  Google Scholar 

  13. Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118(14):3785–93. https://doi.org/10.1182/blood-2011-04-347229.

    Article  CAS  PubMed  Google Scholar 

  14. Pastoret C, Houot R, Llamas-Gutierrez F, Boulland ML, Marchand T, Tas P, et al. Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing. Leuk Lymphoma. 2017;58(4):1008–12. https://doi.org/10.1080/10428194.2016.1225208. Present potential targetable mutations in myeloid sarcoma.

    Article  PubMed  Google Scholar 

  15. Kashofer K, Gornicec M, Lind K, Caraffini V, Schauer S, Beham-Schmid C, et al. Detection of prognostically relevant mutations and translocations in myeloid sarcoma by next generation sequencing. Leuk Lymphoma. 2018;59(2):501–4. https://doi.org/10.1080/10428194.2017.1339879.

    Article  CAS  PubMed  Google Scholar 

  16. Fouillet L, Daguenet E, Guyotat D, Campos-Guyotat L, Grange R, Cornillon J, et al. A complex mutational profile and a distinct clonal evolution during NPM1 myeloid sarcoma. Leuk Lymphoma. 2019;60(9):2328–30. https://doi.org/10.1080/10428194.2019.1571199.

    Article  PubMed  Google Scholar 

  17. Wang J, Ye X, Fan C, Zhou J, Luo S, Jin J, et al. Leukemia cutis with IDH1, DNMT3A and NRAS mutations conferring resistance to venetoclax plus 5-azacytidine in refractory AML. Biomark Res. 2020;8(1):65. https://doi.org/10.1186/s40364-020-00246-9.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Werstein B, Dunlap J, Cascio MJ, Ohgami RS, Fan G, Press R, et al. Molecular discordance between myeloid sarcomas and concurrent bone marrows occurs in actionable genes and is associated with worse overall survival. J Mol Diagn. 2020;22(3):338–45. https://doi.org/10.1016/j.jmoldx.2019.11.004.

    Article  CAS  PubMed  Google Scholar 

  19. Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299–312. https://doi.org/10.1038/s41375-018-0357-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia. 2003;17(9):1738–52. https://doi.org/10.1038/sj.leu.2403099.

    Article  CAS  PubMed  Google Scholar 

  21. Kennedy VE, Smith CC. FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies. Front Oncol. 2020;10:612880. https://doi.org/10.3389/fonc.2020.612880.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Klug LR, Kent JD, Heinrich MC. Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases. Pharmacol Ther. 2018;191:123–34. https://doi.org/10.1016/j.pharmthera.2018.06.016.

    Article  CAS  PubMed  Google Scholar 

  23. Newell LF, Cook RJ. Advances in acute myeloid leukemia. BMJ. 2021;375:n2026. https://doi.org/10.1136/bmj.n2026.

    Article  PubMed  Google Scholar 

  24. Thol F, Ganser A. Treatment of relapsed acute myeloid leukemia. Curr Treat Options Oncol. 2020;21(8):1–11. https://doi.org/10.1007/s11864-020-00765-5.

    Article  Google Scholar 

  25. Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1–2 study. Lancet Oncol. 2017;18(8):1061–75. https://doi.org/10.1016/S1470-2045(17)30416-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381(18):1728–40. https://doi.org/10.1056/NEJMoa1902688.

    Article  CAS  PubMed  Google Scholar 

  27. Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, et al. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022;139(23):3366–75. https://doi.org/10.1182/blood.2021011583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rollig C, Serve H, Huttmann A, Noppeney R, Muller-Tidow C, Krug U, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015;16(16):1691–9. https://doi.org/10.1016/S1470-2045(15)00362-9.

    Article  CAS  PubMed  Google Scholar 

  29. Chen X, Huang J, Xu N, Fan Z, Nie D, Huang F, et al. A phase 2 study of sorafenib combined with conventional therapies in refractory central nervous system leukemia. Cancer. 2022;128(11):2138–47. https://doi.org/10.1002/cncr.34182. A Phase II clinical study of sorafenib for refractory central nervous system leukemia resulted in an overall CR rate of 80.8% and an ORR of 88.5%.

    Article  CAS  PubMed  Google Scholar 

  30. Arrigo G, D’Ardia S, Audisio E, Cerrano M, Freilone R, Giai V, et al. Gilteritinib in isolated breast relapse of FLT3positive acute myeloid leukemia: a case report and review of literature. Acta Haematol. 2022;145(5):566–70. https://doi.org/10.1159/000524878.

    Article  PubMed  Google Scholar 

  31. Brodie R, Langabeer SE, Quinn J, McMenamin ME, Hayden PJ. Sorafenib for relapsed FLT3-ITD-positive acute myeloid leukemia postallogeneic stem cell transplantation presenting as leukemia cutis. Clin Case Rep. 2019;7(12):2579–80. https://doi.org/10.1002/ccr3.2487.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ogawara Y, Katsumoto T, Aikawa Y, Shima Y, Kagiyama Y, Soga T, et al. IDH2 and NPM1 mutations cooperate to activate Hoxa9/Meis1 and hypoxia pathways in acute myeloid leukemia. Cancer Res. 2015;75(10):2005–16. https://doi.org/10.1158/0008-5472.CAN-14-2200.

    Article  CAS  PubMed  Google Scholar 

  33. Kickingereder P, Sahm F, Radbruch A, Wick W, Heiland S, Deimling A, et al. IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma. Sci Rep. 2015;5:16238. https://doi.org/10.1038/srep16238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cancer Genome Atlas Research N, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. https://doi.org/10.1056/NEJMoa1301689.

    Article  CAS  Google Scholar 

  35. McMurry H, Fletcher L, Traer E. IDH inhibitors in AML-promise and pitfalls. Curr Hematol Malig Rep. 2021;16(2):207–17. https://doi.org/10.1007/s11899-021-00619-3.

    Article  PubMed  Google Scholar 

  36. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67. https://doi.org/10.1016/j.ccr.2010.11.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Marcucci G, Maharry K, Wu YZ, Radmacher MD, Mrozek K, Margeson D, et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol. 2010;28(14):2348–55. https://doi.org/10.1200/JCO.2009.27.3730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xu X, Zhao J, Xu Z, Peng B, Huang Q, Arnold E, et al. Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity. J Biol Chem. 2004;279(32):33946–57. https://doi.org/10.1074/jbc.M404298200.

    Article  CAS  PubMed  Google Scholar 

  39. Martelli MP, Martino G, Cardinali V, Falini B, Martinelli G, Cerchione C. Enasidenib and ivosidenib in AML. Minerva Med. 2020;111(5):411–26. https://doi.org/10.23736/S0026-4806.20.07024-X.

    Article  PubMed  Google Scholar 

  40. Fan B, Le K, Manyak E, Liu H, Prahl M, Bowden CJ, et al. Longitudinal pharmacokinetic/pharmacodynamic profile of AG-120, a potent inhibitor of the IDH1 mutant protein, in a phase 1 study of IDH1-mutant advanced hematologic malignancies. Blood. 2015;126(23):1310. https://doi.org/10.1182/blood.V126.23.1310.1310.

    Article  Google Scholar 

  41. DiNardo C, de Botton S, Pollyea DA, Stein EM, Fathi AT, Roboz GJ, et al. Molecular profiling and relationship with clinical response in patients with IDH1 mutation-positive hematologic malignancies receiving AG-120, a first-in-class potent inhibitor of mutant IDH1, in addition to data from the completed dose escalation portion of the phase 1 study. Blood. 2015;126(23):1306. https://doi.org/10.1182/blood.V126.23.1306.1306.

    Article  Google Scholar 

  42. DiNardo CD, de Botton S, Stein EM, Roboz GJ, Swords RT, Pollyea DA, et al. Determination of IDH1 mutational burden and clearance via next-generation sequencing in patients with IDH1 mutation-positive hematologic malignancies receiving AG-120, a first-in-class inhibitor of mutant IDH1. Blood. 2016;128(22):1070. https://doi.org/10.1182/blood.V128.22.1070.1070.

    Article  Google Scholar 

  43. Roboz GJ, DiNardo CD, Stein EM, de Botton S, Mims AS, Prince GT, et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020;135(7):463–71. https://doi.org/10.1182/blood.2019002140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–31. https://doi.org/10.1182/blood-2017-04-779405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Choi M, Jeon YK, Sun CH, Yun HS, Hong J, Shin DY, et al. RTK-RAS pathway mutation is enriched in myeloid sarcoma. Blood Cancer J. 2018;8(5):43. https://doi.org/10.1038/s41408-018-0083-6.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ball S, Knepper TC, Deutsch YE, Samra W, Watts JM, Bradley TJ, et al. Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations. Cancer. 2022;128(21):3880–7. https://doi.org/10.1002/cncr.34459. In this multicenter retrospective study, next-generation sequencing was used to analyze 58 patients with extramedullary acute myeloid leukemia, and at least one targetable or potentially targetable alteration was found in 52% of patients.

    Article  CAS  PubMed  Google Scholar 

  47. Gupta L, Levoska MA, Sharma T, Honda K, Prendes MA. Bilateral periorbital leukemia cutis presenting as suspected cellulitis. Orbit. 2022;41(4):506–8. https://doi.org/10.1080/01676830.2021.1893343.

    Article  PubMed  Google Scholar 

  48. Lee D, Omofoye OA, Karnati T, Graff JP, Shahlaie K. Intracranial myeloid sarcoma presentation in distant acute myeloid leukemia remission. J Clin Neurosci. 2021;89:158–60. https://doi.org/10.1016/j.jocn.2021.05.001.

    Article  CAS  PubMed  Google Scholar 

  49. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324–37. https://doi.org/10.1038/sj.onc.1210220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202–8. https://doi.org/10.1038/nm.3048.

    Article  CAS  PubMed  Google Scholar 

  51. Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov. 2017;16(4):273–84. https://doi.org/10.1038/nrd.2016.253.

    Article  CAS  PubMed  Google Scholar 

  52. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29. https://doi.org/10.1056/NEJMoa2012971.

    Article  CAS  PubMed  Google Scholar 

  53. Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137–45. https://doi.org/10.1182/blood.2020004856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lou Y, Shao L, Mao L, Lu Y, Ma Y, Fan C, et al. Efficacy and predictive factors of venetoclax combined with azacitidine as salvage therapy in advanced acute myeloid leukemia patients: a multicenter retrospective study. Leuk Res. 2020;91:106317. https://doi.org/10.1016/j.leukres.2020.106317.

    Article  CAS  PubMed  Google Scholar 

  55. Aldoss I, Yang D, Aribi A, Ali H, Sandhu K, Al Malki MM, et al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica. 2018;103(9):e404–7. https://doi.org/10.3324/haematol.2018.188094.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421–8. https://doi.org/10.1158/0008-5472.CAN-07-5836.

    Article  CAS  PubMed  Google Scholar 

  57. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012;30(5):488–96. https://doi.org/10.1200/JCO.2011.34.7898.

    Article  CAS  PubMed  Google Scholar 

  58. Otoukesh S, Zhang J, Nakamura R, Stein AS, Forman SJ, Marcucci G, et al. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement. Leuk Lymphoma. 2020;61(8):2020–3. https://doi.org/10.1080/10428194.2020.1742908. A cohort study of 18 patients with myeloid sarcoma treated with VEN and hypomethylating agents obtained an ORR of 45%.

    Article  CAS  PubMed  Google Scholar 

  59. Pan W, Zhao X, Shi W, Jiang Z, Xiao H. Venetoclax induced complete remission in extramedullary relapse of AML co-harboring NPM1, TET2, and NRAS mutations after haploidentical hematopoietic stem cell transplantation. Leuk Lymphoma. 2020;61(11):2756–9. https://doi.org/10.1080/10428194.2020.1779255.

    Article  CAS  PubMed  Google Scholar 

  60. Mandhan N, Yassine F, Li K, Badar T. Bladder myeloid sarcoma with TP53 mutated myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome: response to decitabine-venetoclax regimen. Leuk Res Rep. 2022;17:100286. https://doi.org/10.1016/j.lrr.2021.100286.

    Article  CAS  PubMed  Google Scholar 

  61. Kanate AS, Vos J, Chargualaf MJ. Venetoclax for refractory myeloid sarcoma. J Oncol Pract. 2019;15(7):413–5. https://doi.org/10.1200/JOP.18.00753.

    Article  PubMed  Google Scholar 

  62. Reda G, Cassin R, Dovrtelova G, Matteo C, Giannotta J, D’Incalci M, et al. Venetoclax penetrates in cerebrospinal fluid and may be effective in chronic lymphocytic leukemia with central nervous system involvement. Haematologica. 2019;104(5):e222–3. https://doi.org/10.3324/haematol.2018.213157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang X, Chen J, Wang W, Li X, Tan Y, Zhang X, et al. Treatment of central nervous system relapse in acute promyelocytic leukemia by venetoclax: a case report. Front Oncol. 2021;11:693670. https://doi.org/10.3389/fonc.2021.693670.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Klossowski S, Miao H, Kempinska K, Wu T, Purohit T, Kim E, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest. 2020;130(2):981–97. https://doi.org/10.1172/JCI129126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. George B, Kantarjian H, Baran N, Krocker JD, Rios A. TP53 in acute myeloid leukemia: molecular aspects and patterns of mutation. Int J Mol Sci. 2021;22(19):10782. https://doi.org/10.3390/ijms221910782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Barbosa K, Li S, Adams PD, Deshpande AJ. The role of TP53 in acute myeloid leukemia: challenges and opportunities. Genes Chromosom Cancer. 2019;58(12):875–88. https://doi.org/10.1002/gcc.22796.

    Article  CAS  PubMed  Google Scholar 

  67. Zhang Q, Bykov VJN, Wiman KG, Zawacka-Pankau J. APR-246 reactivates mutant p53 by targeting cysteines 124 and 277. Cell Death Dis. 2018;9(5):439. https://doi.org/10.1038/s41419-018-0463-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021;39(14):1584–94. https://doi.org/10.1200/JCO.20.02341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cluzeau T, Sebert M, Rahme R, Cuzzubbo S, Lehmann-Che J, Madelaine I, et al. Eprenetapopt plus azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a phase II study by the Groupe Francophone des Myelodysplasies (GFM). J Clin Oncol. 2021;39(14):1575–83. https://doi.org/10.1200/JCO.20.02342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018;18(3):153–67. https://doi.org/10.1038/nri.2017.108.

    Article  CAS  PubMed  Google Scholar 

  71. Kawamoto K, Miyoshi H, Suzuki T, Kiyasu J, Yokoyama S, Sasaki Y, et al. Expression of programmed death ligand 1 is associated with poor prognosis in myeloid sarcoma patients. Hematol Oncol. 2018;36(3):591–9. https://doi.org/10.1002/hon.2506. Expression of PD-L1 on stromal cells within the tumor microenvironment was found to be associated with poorer overall survival and progression-free survival and was also identified as an independent poor prognostic factor.

    Article  CAS  PubMed  Google Scholar 

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Medical and Health Science and Technology Project of Zhejiang Province(2023RC107), Cultivation of High-Level Innovative Health Talents of Zhejiang Province.

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Fu, L., Zhang, Z., Chen, Z. et al. Gene Mutations and Targeted Therapies of Myeloid Sarcoma. Curr. Treat. Options in Oncol. 24, 338–352 (2023). https://doi.org/10.1007/s11864-023-01063-6

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