Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

Article  PubMed  PubMed Central  Google Scholar 

Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N. Engl J Med. 2018;378:1189–99.

Article  CAS  PubMed  Google Scholar 

Shlush LI, Mitchell A, Heisler L, Abelson S, Ng SWK, Trotman-Grant A, et al. Tracing the origins of relapse in acute myeloid leukaemia to stem cells. Nature. 2017;547:104–8.

Article  CAS  PubMed  Google Scholar 

Stelmach P, Trumpp A. Leukemic stem cells and therapy resistance in acute myeloid leukemia. Haematologica. 2023;108:353–66.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011;17:1086–93.

Article  CAS  PubMed  Google Scholar 

Ng SW, Mitchell A, Kennedy JA, Chen WC, McLeod J, Ibrahimova N, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature. 2016;540:433–37.

Article  CAS  PubMed  Google Scholar 

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–48.

Article  CAS  PubMed  Google Scholar 

Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–37.

Article  CAS  PubMed  Google Scholar 

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

Article  CAS  PubMed  Google Scholar 

van 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.

Article  PubMed  PubMed Central  Google Scholar 

Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25:1315–21.

Article  CAS  PubMed  Google Scholar 

Valent P, Sadovnik I, Eisenwort G, Bauer K, Herrmann H, Gleixner KV, et al. Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML. Int J Mol Sci. 2019;20:4233.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang CC, Yan Z, Pascual B, Jackson-Fisher A, Huang DS, Zong Q, et al. Gemtuzumab Ozogamicin (GO) Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia. Neoplasia. 2018;20:1–11.

Article  PubMed  Google Scholar 

Jiang YP, Liu BY, Zheng Q, Panuganti S, Chen R, Zhu J, et al. CLT030, a leukemic stem cell-targeting CLL1 antibody-drug conjugate for treatment of acute myeloid leukemia. Blood Adv. 2018;2:1738–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zheng B, Yu SF, Del Rosario G, Leong SR, Lee GY, Vij R, et al. An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia. Clin Cancer Res. 2019;25:1358–68.

Article  CAS  PubMed  Google Scholar 

Dutta D, Pan P, Fleming R, Andrade-Campos M, Belova E, Wheeler J, et al. First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors. Blood. 2023;142:5957–57.

Article  Google Scholar 

Stelte-Ludwig B, Schomber T, Izumi R, Wong H, Frigault MM, Rebstock A-S, et al. Selectivity and Safety of VIP943: A Novel CD123-Targeting Antibody-Drug Conjugate (ADC) Using a Proprietary Linker and Payload Class. Blood. 2023;142:1435–35.

Article  Google Scholar 

Li F, Sutherland MK, Yu C, Walter RB, Westendorf L, Valliere-Douglass J, et al. Characterization of SGN-CD123A, A Potent CD123-Directed Antibody–Drug Conjugate for Acute Myeloid Leukemia. Mol Cancer Therapeutics. 2018;17:554–64.

Article  CAS  Google Scholar 

Kovtun Y, Jones GE, Adams S, Harvey L, Audette CA, Wilhelm A, 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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

van der Lee M, van Achtenberg T, Brouwers-Vos A, van der Vleuten M, Kappers W, Verheijden G, et al. Potent in Vitro and In Vivo Efficacy of BYON4413, a Duba-Based Antibody-Drug Conjugate Targeting CD123 in Acute Myeloid Leukemia. Blood. 2023;142:2795.

Article  Google Scholar 

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

Article  CAS  PubMed  Google Scholar 

Brauchle B, Goldstein RL, Karbowski CM, Henn A, Li C-M, Bücklein VL, et al. Characterization of a Novel FLT3 BiTE Molecule for the Treatment of Acute Myeloid Leukemia. Mol Cancer Therapeutics. 2020;19:1875–88.

Article  CAS  Google Scholar 

Yeung YA, Krishnamoorthy V, Dettling D, Sommer C, Poulsen K, Ni I, et al. An Optimized Full-Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-leukemia Activity and Reversible Hematological Toxicity. Mol Ther. 2020;28:889–900.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoshimoto G, Miyamoto T, Jabbarzadeh-Tabrizi S, Iino T, Rocnik JL, Kikushige Y, et al. FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation. Blood. 2009;114:5034–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Levis M. Midostaurin approved for FLT3-mutated AML. Blood. 2017;129:3403–06.

Article  CAS  PubMed  Google Scholar 

Pulte ED, Norsworthy KJ, Wang Y, Xu Q, Qosa H, Gudi R, et al. FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. Clin Cancer Res. 2021;27:3515–21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401:1571–83.

Article  CAS  PubMed  Google Scholar 

Jetani H, Garcia-Cadenas I, Nerreter T, Thomas S, Rydzek J, Meijide JB, et al. CAR T-cells targeting FLT3 have potent activity against FLT3(-)ITD(+) AML and act synergistically with the FLT3-inhibitor crenolanib. Leukemia. 2018;32:1168–79.

Article  CAS  PubMed  Google Scholar 

Roas M, Vick B, Kasper MA, Able M, Polzer H, Gerlach M, et al. Targeting FLT3 with a new-generation antibody-drug conjugate in combination with kinase inhibitors for treatment of AML. Blood. 2023;141:1023–35.

Article  CAS  PubMed  Google Scholar 

Yao H-P, Zhao H, Hudson R, Tong X-M, Wang M-H. Duocarmycin-based antibody–drug conjugates as an emerging biotherapeutic entity for targeted cancer therapy: Pharmaceutical strategy and clinical progress. Drug Discov Today. 2021;26:1857–74.

Article  CAS  PubMed  Google Scholar 

Marcucci F, Caserta CA, Romeo E, Rumio C. Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)-Is There Still Room for Optimism? Front Oncol. 2019;9:167.