acute myeloid leukemia

Overview

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy arising from the clonal expansion of myeloid precursor cells with impaired differentiation and uncontrolled proliferation. It is biologically diverse, with disease behavior shaped by somatic mutations, cytogenetic abnormalities, epigenetic dysregulation, and interactions with the bone marrow niche. Clinically, AML is associated with rapid disease progression, frequent relapse, and substantial treatment resistance, particularly in older adults and in molecularly high-risk subtypes such as FLT3-mutated or TP53-mutated disease.

From a therapeutic perspective, AML is a major focus of precision oncology and translational hematology. Recent work has emphasized pathways involving FLT3, BCL2, PI3K, LSD1, ENL, PIM kinases, METTL1/m7G RNA modification, and epigenetic regulators such as p300/CBP. The disease is also increasingly studied in the context of immune evasion, metabolic reprogramming, leukemia stem cell maintenance, and extramedullary or sanctuary-site involvement, including the central nervous system and liver.

Focus of Latest Publications

Recent publications portray AML as a biologically complex and therapeutically challenging disease, with research spanning targeted therapy, immunotherapy, transplantation, drug delivery, and disease modeling. Several studies focused on FLT3 as a central therapeutic target. FLT3 internal tandem duplication (FLT3-ITD) mutations were described as a major driver of AML, and multiple papers examined FLT3 inhibition, including gilteritinib maintenance after allogeneic transplantation, quizartinib-based treatment, and novel FLT3 inhibitors designed to overcome resistance mutations such as F691L. Another study reported that CD135 (FLT3 receptor) expression on AML blasts may have prognostic value, reinforcing the clinical relevance of this pathway.

Epigenetic and transcriptional dependencies were also prominent. LSD1 was investigated as a therapeutic target because of its role in histone modification and AML pathogenesis, with multiple inhibitor-design studies aiming to improve selectivity and bioavailability. ENL, a YEATS-domain acyl-lysine reader, was identified as a critical dependency in AML, and a highly potent ENL degrader was developed. Additional work highlighted p300/CBP inhibition in combination with gilteritinib and venetoclax as a strategy to target leukemia stem cells in epigenetic mutant AML, while integrated multi-omics analyses described a core epigenetically activated transcriptional network driving oncogenic signaling. METTL1 and its m7G RNA-modification axis were also reported as a druggable epitranscriptomic target linked to leukemia stem cell homeostasis.

Metabolic and survival pathways were another major theme. Venetoclax, a BCL2 inhibitor, appeared repeatedly as a backbone therapy in newly diagnosed unfit patients, older adults, and salvage settings, often combined with hypomethylating agents such as azacitidine or with cytarabine-based regimens. Studies also examined mitochondrial oxidative phosphorylation (OXPHOS) inhibition, metabolic reprogramming, and T-cell exhaustion as determinants of response. MO-IPS was reported to suppress AML through metabolic reprogramming and to synergize with anti-PD-1 immunotherapy, while rosuvastatin was described as enhancing venetoclax-azacitidine efficacy by reducing T-cell exhaustion. Other work linked translation inhibition, mTOR signaling, and HSP90 inhibition to AML cell sensitivity, especially in TP53-mutant disease.

The bone marrow microenvironment and extramedullary dissemination were recurring topics. Several studies emphasized that AML cells persist within a protective bone marrow niche that limits drug bioavailability and promotes resistance. Nanomedicine approaches were developed to improve marrow delivery, including siRNA-loaded lipid nanoparticles, baiting-enhanced extravasation systems, and bone-targeting nanocarriers. Extramedullary disease was reported to occur in a substantial minority of cases and to be associated with poor survival, while Mesothelin expression was linked to a higher risk of extramedullary disease through adhesion and metastasis-related mechanisms. Separate work addressed leukemic liver infiltration and chemotherapy-induced hepatotoxicity using a DPHV-liver module, and CNS involvement was described as rare but high-risk, with allogeneic hematopoietic stem cell transplantation offering curative potential.

Immunotherapy and cellular therapy were also heavily represented. CD33-directed CAR-T approaches, including donor-derived anti-CD33 CAR T-cell therapy, were developed for relapsed/refractory AML after transplantation. A nanobody-based TCR-like CAR-T strategy targeting PRAME was proposed to address the lack of AML-specific surface antigens. Other studies evaluated off-the-shelf allogeneic natural killer cell products and CD37-targeting antibody-drug conjugates, reflecting ongoing efforts to expand immunotherapeutic options in AML. The bone marrow niche was repeatedly described as a barrier to immune and drug efficacy, motivating strategies that enhance retention, trafficking, or local activity.

Transplantation remained central to curative-intent therapy. Studies examined allogeneic hematopoietic stem cell transplantation in high-risk AML, relapse after first transplantation, cord blood transplantation, and conditioning regimens incorporating venetoclax, fludarabine, melphalan, busulfan, thiotepa, or anti-CD117 antibody-based approaches. Outcomes were also reported for AML with CNS involvement and for relapse after transplantation, underscoring the persistent challenge of post-transplant disease control. In parallel, real-world analyses and prognostic modeling studies used mutational and cytogenetic data to refine risk stratification, including in patients treated with venetoclax-based regimens or lower-intensity therapy.

Several publications addressed AML as a disease of older adults and of therapy-related or secondary origin. CPX-351 was revisited in the context of myelodysplasia-related mutations, and AML arising after myeloproliferative neoplasms was associated with poor outcomes. PARP inhibitor exposure was examined in relation to secondary MDS/AML risk in ovarian cancer. Other studies focused on TP53-mutated AML, ASXL1-mutated AML, and NUP98::TOP1-rearranged disease, all of which were described as aggressive or treatment-refractory subtypes.

Key Publications

• Jun Targeting the METTL1/m7G axis as a therapeutic strategy in myeloid leukemia. (Blood, 2026, PMID 42247311): "Together, our findings establish a previously unrecognized role for METTL1 and its target tRNAPheGAA in LSC homeostasis and provide compelling proof-of-concept evidence that METTL1 is a druggable epitranscriptomic target for antileukemia therapy."
• Jun MO-IPS suppresses acute myeloid leukemia through metabolic reprogramming and synergizes with anti-PD-1 immunotherapy. (Functional & integrative genomics, 2026, PMID 42307804): "Collectively, our work repositions MO-IPS from a cytotoxic MYC-PRMT inhibitor to a multifaceted immunometabolic therapeutic."
• Jun A DPHV-liver module recapitulates AML infiltration and chemotherapy-induced hepatotoxicity with translational utility. (Science advances, 2026, PMID 42284417): "In acute myeloid leukemia (AML), patients frequently develop leukemic liver infiltration and chemotherapy-induced hepatotoxicity, both of which compromise therapeutic efficacy and prognosis."
• Apr Targeting BCL-2 and PI3K signaling pathways enhances cytotoxicity of gemtuzumab ozogamicin against acute myeloid leukemia cells. (Biochemical and biophysical research communications, 2026, PMID 41980559): "GO was the first antibody-drug conjugate (ADC) approved for the treatment of patients with CD33+ acute myeloid leukemia (AML)."
• Jun Baiting-enhanced extravasation of lipid nanoparticles for targeted co-delivery of decitabine and siTNF-α to the bone marrow niche in leukemia therapy. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41905408): "Acute myeloid leukemia (AML) remains a fatal malignancy with poor prognosis due to limited drug bioavailability and therapeutic resistance within the protective bone marrow niche."
• Jun MSLN expression predicts a high risk of EMD in AML by promoting cell adhesion and metastasis via interaction with MUC16. (Blood advances, 2026, PMID 41824794): "The overall incidence of extramedullary disease (EMD) in acute myeloid leukemia (AML) ranges from 2% to 30.5%, and is potentially associated with short overall survival."
• Jun Novel staurosporine-type indolocarbazole glycoalkaloids as potent and selective FLT3-ITD inhibitors for acute myeloid leukemia. (European journal of medicinal chemistry, 2026, PMID 41889033): "Aberrant activation of the FMS-like tyrosine kinase 3 (FLT3) caused by internal tandem duplication (ITD) mutations is a major driver of acute myeloid leukemia (AML)."
• Jun Design and optimization of selective and potent LSD1 inhibitors with tranylcypromine-pyrimidine scaffold for the treatment of acute myeloid leukemia. (Bioorganic chemistry, 2026, PMID 41671737): "Lysine-specific demethylase 1 (LSD1), a key epigenetic regulator mediating histone modification, has been a potential therapeutic target for acute myeloid leukemia (AML) due to its critical role in disease pathogenesis."
• Jun CPSM: An R Package for Cancer Patient Survival Risk Model Using Transcriptomics and Clinical Data. (GigaScience, 2026, PMID 42233233): "We demonstrate the utility of CPSM using publicly available TCGA datasets for four cancer types: glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), pancreatic adenocarcinoma (PAAD) and breast invasive cancer (BRCA)."
• Jun Real-world experience with gilteritinib maintenance following allogeneic transplantation in relapsed/refractory AML patients harboring FLT3 mutations. (Blood research, 2026, PMID 42230462): "Gilteritinib is an established FLT3 inhibitor used to treat patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) harboring FLT3 mutations."