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Acute Myeloid Leukemia in Adults (2nd Edition)

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Dear Colleagues,

Acute myeloid leukemia is the most common type of leukemia in adults. It is caused by the acquisition of somatic mutations in hematopoietic stem and progenitor cells mediating their transformation to malignant cells that dominate the bone marrow. Despite extensive investigation of the molecular biology of AML and the introduction of numerous novel agents and combinational approaches for the treatment of this disease, AML patient outcomes—particularly for older individuals and those with antecedent myeloid neoplasms—remain poor. A deeper understanding of the molecular pathways driving AML growth and treatment resistance is needed to guide the development of new therapies, especially for resistant and relapsed forms of AML. This can be achieved by collaborative approaches in AML research and better insight into patterns of resistance to current therapeutic approaches.

This Special Issue will highlight recent discoveries in AML biology, the current therapeutic landscape, and possible mechanisms of resistance to existing treatments. Contributions may include basic, translational, and clinical studies, with particular emphasis on relapsed and treatment-resistant AML.

Dr. Theodoros Karantanos
Guest Editor

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15 pages, 2854 KB

Open AccessArticle

Impact of Fusion Partners and Transplantation Benefit in Intensively Treated KMT2A-Rearranged Acute Myeloid Leukemia

by Heng Shen, Jiayuan Chen, Xiaoyuan Gong, Chunlin Zhou, Dong Lin, Kaiqi Liu, Benfa Gong, Guangji Zhang, Yan Li, Yuntao Liu, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Qiuyun Fang, Jianxiang Wang and Hui Wei

Cancers 2026, 18(3), 401; https://doi.org/10.3390/cancers18030401 - 27 Jan 2026

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Abstract

Background: KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment. Methods: In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring KMT2A rearrangements were analyzed. We used FISH, RT-PCR, and next-generation sequencing, including transcriptome and targeted panels, for diagnosis and mutation profiling. All patients received intensive chemotherapy. We evaluated overall survival and event-free survival using Kaplan–Meier and Cox regression models, with HSCT analyzed as a time-dependent variable. Results: The incidence of KMT2A-rearranged AML in our newly diagnosed cohort was 5.9%. Among the 181 patients included in the final analysis, 89 (49.2%) were male and 92 (50.8%) were female, with a median age of 33 years (range: 13–65). The distribution of fusion partners included KMT2A::MLLT3 (n = 39), KMT2A::AFDN (n = 27), KMT2A::MLLT10 (n = 25), KMT2A::ELL (n = 24), and others (n = 12). Seventy-four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). The median follow-up for survivors was 17.53 months (range 1.47–112.57), and the 3-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 42.0% and 32.1%, respectively. Patients with KMT2A::ELL exhibited superior OS compared to other subtypes (3-year OS [ELL vs. non-ELL]: 59.8% vs. 39.3%, p = 0.023). Concomitant mutations did not significantly impact the prognosis of KMT2A-rearranged AML patients. In multivariate analysis, age and HSCT in CR1 were independently associated with OS and EFS (OS: HR = 1.022, p = 0.026 [age]; HR = 0.238, p < 0.001 [HSCT]; EFS: HR = 1.027, p = 0.002 [age]; HR = 0.155, p < 0.001 [HSCT]). Patients aged over 20 years were more likely to benefit from HSCT than those aged 20 years or younger (p < 0.001 [age > 20], p = 0.780 [age ≤ 20]). Conclusions: Our study revealed the heterogeneous outcomes of KMT2A-rearranged AML patients and clarified the impact of HSCT across different age groups. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults (2nd Edition))

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27 pages, 433 KB

Open AccessReview

Integrating Targeted Therapies into AML Frontline Therapy: Who Gets What and What Does the Future Hold?

by Johanna Schreiber, Georg Hopfinger and Karoline V. Gleixner

Cancers 2026, 18(6), 1034; https://doi.org/10.3390/cancers18061034 - 23 Mar 2026

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Abstract

For decades, induction treatment of acute myeloid leukemia consisted of intensive chemotherapy for induction. High relapse rates and severe toxicity resulted in a five-year overall survival of ~30%. In patients ineligible for intensive treatment, hypomethylating agents (HMA) could be administered but generally failed to induce durable remissions. These limitations have driven the development of targeted drugs and less toxic therapeutic regimens. In the past decade, fourteen new agents have gained FDA and/or EMA approval, including small-molecule inhibitors targeting FLT3, IDH1, IDH2, BCL-2, menin, and the hedgehog pathway, as well as a CD33-directed antibody-drug conjugate. The combination of targeted drugs with intensive chemotherapy or HMA has resulted in improved remission rates and prolonged survival in certain patient subpopulations. However, many promising combinations are currently being evaluated in randomized trials and are not yet available in clinical routine. A combination that has become standard of care is HMA plus venetoclax for patients unfit for intensive chemotherapy, achieving high remission rates with relatively manageable toxicity. Moreover, targeted drugs directed against FLT3 and IDH1 have been approved in combination with intensive chemotherapy and HMA, respectively. Clinical decision-making requires rapid molecular diagnostic testing, assessment of a patient’s fitness for intensive chemotherapy, and management of toxicities and drug interactions. This narrative review, illustrated with patient vignettes, summarizes currently available therapies, guides through the latest trials on frontline combinations in AML, and provides a preview of how the therapeutic landscape may evolve in the near future. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults (2nd Edition))

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