Core Viewpoint - Acute Myeloid Leukemia (AML) is a heterogeneous malignancy with poor prognosis due to relapse and chemotherapy resistance, making FLT3 mutations a promising therapeutic target [2][3]. Group 1: AML Overview - AML is driven by various genetic mutations, with a 5-year survival rate of only 30%-35% due to non-selective cytotoxic chemotherapy leading to severe side effects and frequent relapses [2]. - Current first-line treatments include cytarabine, daunorubicin, and idarubicin, but there is a need for more selective therapies [2]. Group 2: FLT3 as a Target - FLT3 is expressed on 70%-100% of AML patient cells, making it an attractive target for antibody-drug conjugates (ADCs) [3]. - Several FLT3-targeting therapeutic antibodies and ADCs have shown promising activity in preclinical studies and are currently under clinical evaluation [3]. Group 3: Recent Research Developments - A study published on September 19, 2025, by a team from Sun Yat-sen University developed a FLT3 ligand-based drug conjugate, FL-Fc-DM1, which effectively targets chemoresistant leukemia stem cells in AML [4][6]. - FL-Fc-DM1 combines FLT3 ligand-Fc with DM1, a potent microtubule assembly inhibitor, demonstrating strong anti-leukemia activity in various models [6]. Group 4: Efficacy and Safety of FL-Fc-DM1 - FL-Fc-DM1 effectively targets cytarabine-resistant AML cells, promoting cell cycle entry and inducing apoptosis while significantly reducing the frequency of functional leukemia stem cells [6][7]. - Toxicity assessments in humanized mouse models indicate that FL-Fc-DM1 has limited impact on normal human hematopoietic function at therapeutic doses, suggesting its potential as a promising candidate for AML treatment [6][7].