REFERENCES

1. Hao T, Li-Talley M, Buck A, Chen W. An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States. Sci Rep 2019;9:12070.

2. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev 2019;36:70-87.

3. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017;7:e577.

4. Teachey DT, Pui C. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol 2019;20:e142-54.

5. Deschler B, Lübbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer 2006;107:2099-107.

6. Stein EM, Tallman MS. Remission induction in acute myeloid leukemia. Int J Hematol 2012;96:164-70.

7. Medeiros BC, Chan SM, Daver NG, Jonas BA, Pollyea DA. Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia. Am J Hematol 2019;94:803-11.

8. Roberts KG. Genetics and prognosis of ALL in children vs adults. Hematol Am Soc Hematol Educ Progr 2018;2018:137-45.

9. Hao T, Van Ha C, Huu Son N, Nhu Hiep P. Long-term outcome of childhood acute myeloid leukemia: a 10-year retrospective cohort study. Pediatr Rep 2020;12:8486.

10. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 1998;339:605-15.

11. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645-8.

12. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3:730-7.

13. Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer stem cells. Int J Biochem Cell Biol 2012;44:2144-51.

14. Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004;5:738-43.

15. Ng SW, Mitchell A, Kennedy JA, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature 2016;540:433-7.

16. Dick JE. Stem cell concepts renew cancer research. Blood 2008;112:4793-807.

17. Hanekamp D, Cloos J, Schuurhuis GJ. Leukemic stem cells: identification and clinical application. Int J Hematol 2017;105:549-57.

18. Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med 2009;15:1010-2.

19. Costello RT, Mallet F, Gaugler B, et al. Human acute myeloid leukemia CD34+/CD38- progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res 2000;60:4403-11.

20. Zeijlemaker W, Grob T, Meijer R, et al. CD34+CD38- leukemic stem cell frequency to predict outcome in acute myeloid leukemia. Leukemia 2019;33:1102-12.

21. Eun K, Ham SW, Kim H. Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Rep 2017;50:117-25.

22. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105-11.

23. Guzman ML, Neering SJ, Upchurch D, et al. Nuclear factor-κB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 2001;98:2301-7.

24. Heidel FH, Arreba-Tutusaus P, Armstrong SA, Fischer T. Evolutionarily conserved signaling pathways: acting in the shadows of acute myelogenous leukemia’s genetic diversity. Clin Cancer Res 2015;21:240-8.

25. Yang X, Yao R, Wang H. Update of ALDH as a potential biomarker and therapeutic target for AML. Biomed Res Int 2018;2018:9192104.

26. Kuo YH, Qi J, Cook GJ. Regain control of p53: targeting leukemia stem cells by isoform-specific HDAC inhibition. Exp Hematol 2016;44:315-21.

27. Vasconcelos FC, de Souza PS, Hancio T, de Faria FCC, Maia RC. Update on drug transporter proteins in acute myeloid leukemia: pathological implication and clinical setting. Crit Rev Oncol Hematol 2021;160:103281.

28. Beauchamp L, Himonas E, Helgason GV. Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia. Leukemia 2021;36:1-12.

29. Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci 2019;234:116781.

30. Wittwer NL, Brumatti G, Marchant C, et al. High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression. Blood Adv 2017;1:1067-79.

31. Andrews TE, Wang D, Harki DA. Cell surface markers of cancer stem cells: diagnostic macromolecules and targets for drug delivery. Drug Deliv Transl Res 2013;3:121-42.

32. Ding Y, Gao H, Zhang Q. The biomarkers of leukemia stem cells in acute myeloid leukemia. Stem cell Investig 2017;4:19.

33. Senft D, Jeremias I. A rare subgroup of leukemia stem cells harbors relapse-inducing potential in acute lymphoblastic leukemia. Exp Hematol 2019;69:1-10.

34. Bernt KM, Armstrong SA. Leukemia stem cells and human acute lymphoblastic leukemia. Semin Hematol 2009;46:33-8.

35. van Rhenen A, Moshaver B, Kelder A, et al. Aberrant marker expression patterns on the CD34+CD38- stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission. Leukemia 2007;21:1700-7.

36. Jordan CT, Upchurch D, Szilvassy SJ, et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 2000;14:1777-84.

37. Taussig DC, Pearce DJ, Simpson C, et al. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood 2005;106:4086-92.

38. Haubner S, Perna F, Köhnke T, et al. Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML. Leukemia 2019;33:64-74.

39. Testa U, Riccioni R, Militi S, et al. Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood 2002;100:2980-8.

40. Cancilla D, Rettig MP, DiPersio JF. Targeting CXCR4 in AML and ALL. Front Oncol 2020;10:1672.

41. Han YC, Kahler J, Piché-Nicholas N, et al. Development of highly optimized antibody-drug conjugates against CD33 and CD123 for acute myeloid leukemia. Clin Cancer Res 2021;27:622.

42. Yu B, Liu D. Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia. Biomark Res 2019;7:24.

43. Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002;415:536-41.

44. Anderson AC, Anderson DE, Bregoli L, et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 2007;318:1141.

45. Sakuishi K, Ngiow SF, Sullivan JM, et al. TIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. Oncoimmunology 2013;2:e23849.

46. Ndhlovu LC, Lopez-Vergès S, Barbour JD, et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 2012;119:3734-43.

47. Kikushige Y, Shima T, Takayanagi S, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell 2010;7:708-17.

48. Jan M, Chao MP, Cha AC, et al. Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci U S A 2011;108:5009-14.

49. Sakoda T, Kikushige Y, Harada T, et al. Evaluation of TIM-3-positive LSCs post Allo-SCT is a highly sensitive strategy to predict AML relapses. Blood 2019;134:2702.

50. Bakker ABH, van den Oudenrijn S, Bakker AQ, et al. C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia. Cancer Res 2004;64:8443-50.

51. van Rhenen A, van Dongen GAMS, Kelder A, et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood 2007;110:2659-66.

52. Wang J, Chen S, Xiao W, et al. CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia. J Hematol Oncol 2018;11:1-13.

53. Ngai LL, Ma CY, Maguire O, et al. Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients. Eur J Haematol 2021;107:343-53.

54. Zheng B, Yu SF, del Rosario G, et al. An anti-CLL-1 antibody-drug conjugate for the treatment of acute myeloid leukemia. Clin Cancer Res 2019;25:1358.

55. Narla RK, Modi H, Wong L, et al. Abstract 4694: The humanized anti-CD47 monclonal antibody, CC-90002, has antitumor activity in vitro and in vivo. Cancer Res 2017;77:4694.

56. Majeti R, Chao MP, Alizadeh AA, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 2009;138:286-99.

57. Liu J, Wang L, Zhao F, et al. Pre-clinical development of a humanized anti-CD47 antibody with anti-cancer therapeutic potential. PLoS One 2015;10:e0137345.

58. Busfield SJ, Biondo M, Wong M, et al. Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC. Leukemia 2014;28:2213-21.

59. Akiyama T, Takayanagi S, Maekawa Y, et al. First preclinical report of the efficacy and PD results of KHK2823, a non-Fucosylated fully human monoclonal antibody against IL-3Rα. Blood 2015;126:1349-1349.

60. Sutherland MK, Yu C, Lewis TS, et al. Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia. MAbs 2009;1:481-90.

61. Schürch CM. Therapeutic antibodies for myeloid neoplasms-current developments and future directions. Front Oncol 2018;8:1.

62. Gramatzki M, Staudinger M, Kellner C, et al. CD96 antibody TH-111 eradicates AML-LSC from autografts and the Fc-engineered variant MSH-TH111e may be used in vivo. Biol Blood Marrow Transplant 2016;22:S200.

63. Chung SS, Eng WS, Hu W, et al. CD99 is a therapeutic target on disease stem cells in myeloid malignancies. Sci Transl Med 2017;9:eaaj2025.

64. Gadhoum SZ, Madhoun NY, Abuelela AF, Merzaban JS. Anti-CD44 antibodies inhibit both mTORC1 and mTORC2: a new rationale supporting CD44-induced AML differentiation therapy. Leukemia 2016;30:2397-401.

65. Kovtun Y, Jones GE, Adams S, et al. A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Adv 2018;2:848-58.

66. Li F, Sutherland MK, Yu C, et al. Characterization of SGN-CD123A, a potent CD123-directed antibody-drug conjugate for acute myeloid leukemia. Mol Cancer Ther 2018;17:554.

67. Gottardi M, Sperotto A, Ghelli Luserna Di Rorà A, et al. Gemtuzumab ozogamicin in acute myeloid leukemia: past, present and future. Minerva Med 2020;111:395-410.

68. Kung Sutherland MS, Walter RB, Jeffrey SC, et al. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 2013;122:1455-63.

69. Flynn MJ, van Berkel P, Zammarchi F, et al. Pre-clinical activity of Adct-301, a novel pyrrolobenzodiazepine (PBD) dimer-containing antibody drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Blood 2014;124:4491.

70. Flynn MJ, Zammarchi F, Tyrer PC, et al. ADCT-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Mol Cancer Ther 2016;15:2709-21.

71. Gao C, Leyton J V, Schimmer AD, Minden M, Reilly RM. Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123(+)/CD131(-) phenotype of leukemia stem cells. Appl Radiat Isot 2016;110:1-7.

72. Jurcic J, Rosenblat T, Mcdevitt M, et al. Targeted alpha-particle nano-generator Actinium-225 (225Ac)-lintuzumab (anti-CD33) in acute myeloid leukemia (AML). Clin Lymphoma Myeloma Leuk 2013;13:S379-80.

73. Chichili GR, Huang L, Li H, et al. A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates. Sci Transl Med 2015;7:289ra82.

74. Hutmacher C, Volta L, Rinaldi F, et al. Development of a novel fully-human anti-CD123 antibody to target acute myeloid leukemia. Leuk Res 2019;84:106178.

75. Krupka C, Kufer P, Kischel R, 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;123:356-65.

76. Subklewe M, Stein A, Walter RB, et al. Preliminary results from a phase 1 first-in-human study of AMG 673, a novel half-life extended (HLE) anti-CD33/CD3 BiTE® (bispecific T-cell engager) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Blood 2019;134:833.

77. Leong SR, Sukumaran S, Hristopoulos M, et al. An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia. Blood 2017;129:609-18.

78. van Loo PF, Hangalapura BN, Thordardottir S, et al. MCLA-117, a CLEC12AxCD3 bispecific antibody targeting a leukaemic stem cell antigen, induces T cell-mediated AML blast lysis. Expert Opin Biol Ther 2019;19:721-33.

79. Boyd-Kirkup J, Thakkar D, Brauer P, Zhou J, Chng W-J, Ingram PJ. HMBD004, a novel anti-CD47xCD33 bispecific antibody displays potent anti-tumor effects in pre-clinical models of AML. Blood 2017;130:1378.

80. Mardiros A, Dos Santos C, McDonald T, et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 2013;122:3138-48.

81. Kenderian SS, Ruella M, Shestova O, et al. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia 2015;29:1637-47.

82. Casucci M, di Robilant B, Falcone L, et al. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 2013;122:3461-72.

83. Gomes-Silva D, Atilla E, Atilla PA, et al. CD7 CAR T cells for the therapy of acute myeloid leukemia. Mol Ther 2019;27:272-80.

84. Wiersma VR, de Bruyn M, Shi C, et al. C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity. MAbs 2015;7:321-30.

85. Madhumathi J, Sridevi S, Verma RS. CD25 targeted therapy of chemotherapy resistant leukemic stem cells using DR5 specific TRAIL peptide. Stem Cell Res 2017;19:65-75.

86. Benmebarek MR, Cadilha BL, Herrmann M, et al. A modular and controllable T cell therapy platform for acute myeloid leukemia. Leukemia 2021;35:2243-57.

87. Liu Y, Wang G, Zhang J, et al. CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia. Stem Cell Res Ther 2021;12:86.

88. Touzet L, Dumezy F, Roumier C, et al. CD9 in acute myeloid leukemia: prognostic role and usefulness to target leukemic stem cells. Cancer Med 2019;8:1279-88.

89. Li H, Zhao N, Li Y, et al. c-MPL is a candidate surface marker and confers self-renewal, quiescence, chemotherapy resistance, and leukemia initiation potential in leukemia stem cells. Stem Cells 2018;36:1685-96.

90. Yoshihara H, Arai F, Hosokawa K, et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 2007;1:685-97.

91. Gils N, Denkers F, Smit L. Escape from treatment; the different faces of leukemic stem cells and therapy resistance in acute myeloid leukemia. Front Oncol 2021;11:659253.

92. Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem 2007;282:20059-63.

93. Gouilleux-gruart V, Gouilleux F, Desaint C, et al. STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. Blood 1996;87:1692-7.

94. Cook AM, Li L, Ho Y, et al. Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells. Blood 2014;123:2826-37.

95. Reikvam H. Inhibition of NF-κB signaling alters acute myelogenous leukemia cell transcriptomics. Cells 2020;9:1677.

96. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998;281:1680.

97. Siveen KS, Mustafa N, Li F, et al. Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget 2014;5:634-48.

98. Ji Q, Ding Y, Sun Y, et al. Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells. Oncotarget 2016;7:40.

99. Estruch M, Vittori C, Montesinos TM, Reckzeh K, Theilgaard-Mönch K. Targeting of PI3K/AKT signaling and DNA damage response in acute myeloid leukemia: a novel therapeutic strategy to boost chemotherapy response and overcome resistance. Cancer Drug Resist 2021;4:984-95.

100. Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 2015;12:445-64.

101. Kim SD, Byun YH, Hur EH, et al. Abstract 4518: Effects of a novel small molecule inhibitor of Wnt signal pathway, CWP232291, on primary tumor cells from patients with malignant hematologic diseases. Cancer Res 2011;71:4518.

102. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012;149:1192-205.

103. Simon M, Grandage VL, Linch DC, Khwaja A. Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia. Oncogene 2005;24:2410-20.

104. Griffiths EA, Gore SD, Hooker C, et al. Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation. Leuk Lymphoma 2010;51:1711-9.

105. Wang Y, Krivtsov AV, Sinha AU, et al. The wnt/β-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010;327:1650-3.

106. Gandillet A, Park S, Lassailly F, et al. Heterogeneous sensitivity of human acute myeloid leukemia to β-catenin down-modulation. Leukemia 2011;25:770-80.

107. Cobas M, Wilson A, Ernst B, et al. Beta-catenin is dispensable for hematopoiesis and lymphopoiesis. J Exp Med 2004;199:221-9.

108. Lenz HJ, Kahn M. Safely targeting cancer stem cells via selective catenin coactivator antagonism. Cancer Sci 2014;105:1087-92.

109. Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol 2020;13:165.

110. Pelullo M, Zema S, Nardozza F, Checquolo S, Screpanti I, Bellavia D. Wnt, Notch, and TGF-β pathways impinge on hedgehog signaling complexity: an open window on cancer. Front Genet 2019;10:711.

111. Gering M, Patient R. Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell 2005;8:389-400.

112. Gao J, Graves S, Koch U, et al. Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 2009;4:548-58.

113. Duncan AW, Rattis FM, DiMascio LN, et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005;6:314-22.

114. Mancini SJ, Mantei N, Dumortier A, Suter U, MacDonald HR, Radtke F. Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. Blood 2005;105:2340-2.

115. Maillard I, Koch U, Dumortier A, et al. Canonical Notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell 2008;2:356-66.

116. Kobune M, Takimoto R, Murase K, et al. Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells. Cancer Sci 2009;100:948-55.

117. Liu N, Zhang J, Ji C. The emerging roles of Notch signaling in leukemia and stem cells. Biomark Res 2013;1:23.

118. Lobry C, Ntziachristos P, Ndiaye-Lobry D, et al. Notch pathway activation targets AML-initiating cell homeostasis and differentiation. J Exp Med 2013;210:301-19.

119. Grieselhuber NR, Klco JM, Verdoni AM, et al. Notch signaling in acute promyelocytic leukemia. Leukemia 2013;27:1548-57.

120. Kode A, Manavalan JS, Mosialou I, et al. Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts. Nature 2014;506:240-4.

121. Kang YA, Pietras EM, Passegué E. Deregulated Notch and Wnt signaling activates early-stage myeloid regeneration pathways in leukemia. J Exp Med 2020;217:e20190787.

122. Canales T, de Leeuw DC, Vermue E, Ossenkoppele GJ, Smit L. Specific depletion of leukemic stem cells: can microRNAs make the difference? Cancers (Basel) 2017;9:74.

123. Balaian L, Kulijian A, Ball ED, Jamieson CHM. Abstract 3338: pacritinib reduces human myeloid leukemia stem cell maintance in a defined niche. Cancer Res 2016;76:3338.

124. Shastri A, Choudhary G, Teixeira M, et al. Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells. J Clin Invest 2018;128:5479-88.

125. Wilde L, Martinez-outschoorn U, Palmisiano N, Kasner M. OPB-111077 in combination with decitabine and venetoclax for the treatment of acute myeloid leukemia. Blood 2019;134:2597.

126. Zhang Q, Hossain DM, Duttagupta P, et al. Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia. Blood 2016;127:1687-700.

127. Wingelhofer B, Maurer B, Heyes EC, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia 2018;32:1135-46.

128. Jiang X, Mak PY, Mu H, et al. Disruption of wnt/b-catenin exerts antileukemia activity and synergizes with flt3 inhibition in flt3-mutant acute myeloid leukemia. Clin Cancer Res 2018;24:2417-29.

129. Benoit YD, Mitchell RR, Risueño RM, et al. Sam68 allows selective targeting of human cancer stem cells. Cell Chem Biol 2017;24:833-44.e9.

130. Fiskus W, Sharma S, Saha S, et al. Pre-clinical efficacy of combined therapy with novel β-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells. Leukemia 2015;29:1267-78.

131. Fong CY, Gilan O, Lam EY, et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 2015;525:538-42.

132. Ye Q, Jiang J, Zhan G, et al. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia. Sci Rep 2016;6:26510.

133. Dongdong Z, Jin Y, Yang T, et al. Antiproliferative and immunoregulatory effects of azelaic acid against acute myeloid leukemia via the activation of notch signaling pathway. Front Pharmacol 2019;10:1396.

134. Arenas A, Lainez D, del Castillo C, et al. Inhibition of the hedgehog pathway decreases the quiescent CD34+CD38- population in acute myeloid leukemia. Blood 2018;132:1509.

135. Fukushima N, Minami Y, Kakiuchi S, et al. Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Cancer Sci 2016;107:1422-9.

136. Li X, Chen F, Zhu Q, et al. Gli-1/PI3K/AKT/NF-kB pathway mediates resistance to radiation and is a target for reversion of responses in refractory acute myeloid leukemia cells. Oncotarget 2016;7:33004-15.

137. Lim Y, Gondek L, Li L, et al. Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia. Sci Transl Med 2015;7:291ra96.

138. Long B, Wang LX, Zheng FM, et al. Targeting GLI1 suppresses cell growth and enhances chemosensitivity in CD34+ enriched acute myeloid leukemia progenitor cells. Cell Physiol Biochem 2016;38:1288-302.

139. Strair RK, Gharibo M, Schaar D, et al. Nuclear factor-κB modulation in patients undergoing induction chemotherapy for acute myelogenous leukemia. Clin Cancer Res 2008;14:7564.

140. Zhou L, Ruvolo VR, McQueen T, et al. HDAC inhibition by SNDX-275 (Entinostat) restores expression of silenced leukemia-associated transcription factors Nur77 and Nor1 and of key pro-apoptotic proteins in AML. Leukemia 2013;27:1358-68.

141. Novotny-Diermayr V, Hart S, Goh KC, et al. The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML. Blood Cancer J 2012;2:e69.

142. Li Y, Chen K, Zhou Y, et al. A new strategy to target acute myeloid leukemia stem and progenitor cells using chidamide, a histone deacetylase inhibitor. Curr Cancer Drug Targets 2015;15:493-503.

143. Yang W, Xie J, Hou R, et al. Disulfiram/cytarabine eradicates a subset of acute myeloid leukemia stem cells with high aldehyde dehydrogenase expression. Leuk Res 2020;92:106351.

144. Venton G, Pérez-Alea M, Baier C, et al. Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors. Blood Cancer J 2016;6:e469.

145. Tavor S, Eisenbach M, Jacob-Hirsch J, et al. The CXCR4 antagonist AMD3100 impairs survival of human AML cells and induces their differentiation. Leukemia 2008;22:2151-5158.

146. Abraham M, Klein S, Bulvik B, et al. The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia 2017;31:2336-46.

147. Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009;113:6215-24.

148. Kuhne MR, Mulvey T, Belanger B, et al. BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clin Cancer Res 2013;19:357.

149. Cox CV, Evely RS, Oakhill A, Pamphilon DH, Goulden NJ, Blair A. Characterization of acute lymphoblastic leukemia progenitor cells. Blood 2004;104:2919-25.

150. Cox CV, Diamanti P, Evely RS, Kearns PR, Blair A. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood 2009;113:3287-96.

151. Handgretinger R, Kuçi S. CD133-positive hematopoietic stem cells: from biology to medicine. Adv Exp Med Biol 2013;777:99-111.

152. Hong D, Gupta R, Ancliff P, et al. Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 2008;319:336.

153. Kong Y, Yoshida S, Saito Y, et al. CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL. Leukemia 2008;22:1207-13.

154. le Viseur C, Hotfilder M, Bomken S, et al. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell 2008;14:47-58.

155. Bardini M, Woll PS, Corral L, et al. Clonal variegation and dynamic competition of leukemia-initiating cells in infant acute lymphoblastic leukemia with MLL rearrangement. Leukemia 2015;29:38-50.

156. Wojcik B, Lang F, Rieger MA. On the hunt for B-cell lymphoblastic leukemia-initiating stem cells. Oncotarget 2017;8:108286-7.

157. Lang F, Wojcik B, Bothur S, et al. Plastic CD34 and CD38 expression in adult B-cell precursor acute lymphoblastic leukemia explains ambiguity of leukemia-initiating stem cell populations. Leukemia 2017;31:731-4.

158. Elder A, Bomken S, Wilson I, et al. Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia. Leukemia 2017;31:2577-86.

159. Cox CV, Martin HM, Kearns PR, Virgo P, Evely RS, Blair A. Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood 2007;109:674-82.

160. Janeway CAJ. The co-receptor function of CD4. Semin Immunol 1991;3:153-60.

161. Gerby B, Clappier E, Armstrong F, et al. Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations. Leukemia 2011;25:1249-58.

162. Chiu PP, Jiang H, Dick JE. Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance. Blood 2010;116:5268-79.

163. Piovan E, Yu J, Tosello V, et al. Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia. Cancer Cell 2013;24:766-76.

164. González-García S, Mosquera M, Fuentes P, et al. IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia. Blood 2019;134:2171-82.

165. Yang J, Ravandi F, Advani A, et al. A phase 1b study of vadastuximab talirine as maintenance and in combination with standard consolidation for patients with acute myeloid leukemia (AML). Blood 2016;128:340.

166. Brierley CK, Staves J, Roberts C, et al. The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia. Transfusion 2019;59:2248-54.

167. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017;376:836-47.

168. Jabbour E, Patel K, Jain N, et al. Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: A post hoc analysis from the phase 3 TOWER study. Am J Hematol 2021;96:E379-83.

169. Advani AS, Moseley A, O’Dwyer KM, et al. SWOG 1318: a phase II trial of blinatumomab followed by POMP maintenance in older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. J Clin Oncol 2022; doi: 10.1200/JCO.21.01766.

170. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018;378:439-48.

171. Ortíz-Maldonado V, Rives S, Castellà M, et al. CART19-BE-01: a multicenter trial of ARI-0001 cell therapy in patients with CD19 + relapsed/refractory malignancies. Mol Ther 2021;29:636-44.

172. Eghtedar A, Verstovsek S, Estrov Z, et al. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood 2012;119:4614-8.

173. Lee JH, Faderl S, Pagel JM, et al. Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome. Blood Adv 2020;4:2032-43.

174. Jeon JY, Zhao Q, Buelow DR, et al. Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2/FLT3 inhibitor, and chemotherapy in FLT3-ITD-positive AML. Invest New Drugs 2020;38:340-9.

175. Heuser M, Smith BD, Fiedler W, et al. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol 2021;100:1181-94.

176. Tibes R, Kosiorek HE, Dueck A, et al. Phase I/IB study of Azacitidine and Hedgehog pathway inhibition with Sonidegib (LDE225) in myeloid malignancies. Blood 2017;130:2629.

177. Zhou HS, Carter BZ, Andreeff M. Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang. Cancer Biol Med 2016;13:248-59.

178. Cox CV, Martin HM, Kearns PR, Virgo P, Evely RS, Blair A. Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood 2007;109:674-82.

179. Zeijlemaker W, Kelder A, Cloos J, Schuurhuis GJ. Immunophenotypic detection of measurable residual (Stem Cell) disease using LAIP approach in acute myeloid leukemia. Curr Protoc Cytom 2019;91:e66.

180. Ngai LL, Kelder A, Janssen JJWM, Ossenkoppele GJ, Cloos J. MRD tailored therapy in AML: what we have learned so far. Front Oncol 2021;10:603636.

181. Yanagisawa B, Ghiaur G, Smith BD, Jones RJ. Translating leukemia stem cells into the clinical setting: harmonizing the heterogeneity. Exp Hematol 2016;44:1130-7.

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