Review
Oncology
Hiroto Ishii, Shingo Yano
Summary: With the advent of new drugs, the prognosis of AML patients with specific genetic mutations has improved. In addition to conventional chemotherapy and transplantation, new treatments and drugs, including CD33-targeting antibody drugs, novel chemotherapies, immunotherapies, and cell-surface antigen-targeted therapies, have emerged.
Review
Oncology
Sargam Kapoor, Grace Champion, Aparna Basu, Anu Mariampillai, Matthew J. Olnes
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow with poor prognosis. Recent advancements in immune therapies, including immune suppressive therapy and novel treatments like monoclonal antibodies and cellular therapeutics, have shown promise in treating these diseases.
Review
Oncology
Justin Loke, Hrushikesh Vyas, Charles Craddock
Summary: AML is the most common indication for allo-SCT worldwide, with advancements in risk stratification, donor availability, and conditioning regimens expanding transplant access for high risk patients. Disease relapse remains the top cause of transplant failure, highlighting the need for novel strategies to reduce recurrence risk.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Fabiana Cacace, Rossella Iula, Danilo De Novellis, Valeria Caprioli, Maria Rosaria D'Amico, Giuseppina De Simone, Rosanna Cuccurullo, William G. Wierda, Kris Michael Mahadeo, Giuseppe Menna, Francesco Paolo Tambaro
Summary: Pediatric acute myeloid leukemia is a clonal disorder characterized by malignant transformation of the hematopoietic stem cell. Treatment includes chemotherapy and stem cell transplantation. Although prognosis has improved, it remains inferior to pediatric acute lymphoblastic leukemia.
Review
Immunology
Johanna Rausch, Evelyn Ullrich, Michael W. M. Kuehn
Summary: AML is a malignant disease that is difficult to treat, especially in patients who cannot undergo intensive chemotherapy. Immunotherapy has been successful in treating solid tumors and lymphatic neoplasms, but its efficacy in AML has been limited. Epigenetic dysregulation is a driver of leukemogenesis, and combining targeted epigenetic drugs with immunotherapy may improve treatment outcomes. Further research is needed to understand the immune functions affected by these drugs and their potential for clinical use.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Rebecca J. Austin, Jasmin Straube, Rohit Halder, Yashaswini Janardhanan, Claudia Bruedigam, Matthew Witkowski, Leanne Cooper, Amy Porter, Matthias Braun, Fernando Souza-Fonseca-Guimaraes, Simone A. Minnie, Emily Cooper, Sebastien Jacquelin, Axia Song, Tobias Bald, Kyohei Nakamura, Geoffrey R. Hill, Iannis Aifantis, Steven W. Lane, Megan J. Bywater
Summary: AML is a genetically heterogeneous and aggressive hematological malignancy caused by distinct oncogenic driver mutations. The impact of specific AML oncogenes on immune response remains uncertain. This study reveals that different AML oncogenes determine immunogenicity, quality of immune response, and immune escape through immunoediting. The findings emphasize the significance of personalized immunotherapies for AML patients.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Wenxin Du, Aixiao Xu, Yunpeng Huang, Ji Cao, Hong Zhu, Bo Yang, Xuejing Shao, Qiaojun He, Meidan Ying
Summary: Autophagy plays a crucial role in the development of AML, with studies indicating the potential of modulating autophagy to enhance targeted therapy for AML.
Review
Oncology
Gaku Oshikawa, Koji Sasaki
Summary: Now that low-intensity therapies have become the leading options for elderly patients, it is crucial to consider age and comorbidities when selecting therapy. Factors influencing mortality and prognosis in patients receiving intensive chemotherapy and the risk categories derived from these factors are reviewed, followed by a discussion of potential treatment options. Low-intensity therapies, such as the combination of a hypomethylating agent with venetoclax, have emerged as promising treatment options for elderly patients. Comorbidity-based risk stratification allows prognosis stratification in patients undergoing both intensive and low-intensity chemotherapy, and optimizing treatment intensity based on such stratification is anticipated to improve the life expectancy for AML patients.
Review
Oncology
A. Bazinet, H. M. Kantarjian
Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Personalized therapy based on patient characteristics and cytogenetic/molecular features is now possible. Intensive or low-intensity treatment approaches can be selected based on patient age and/or comorbidities. Molecularly defined AML subtypes benefit from targeted agents, while novel therapies are needed for TP53-mutated AML. Optimization of AML therapy in patients without actionable mutations and the role of measurable residual disease in modifying therapy are also discussed.
ANNALS OF ONCOLOGY
(2023)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Review
Biochemistry & Molecular Biology
Rikako Tabata, SungGi Chi, Junichiro Yuda, Yosuke Minami
Summary: Studies have suggested the potential clinical benefits of immuno-oncology therapy against AML, including immune checkpoint inhibitors and bi-/tri-specific antibodies. CAR-T and NK cells have shown effectiveness for relapsed/refractory AML patients, and conventional chemotherapy combined with anti-PD-1/anti-CTLA4 antibodies also demonstrated certain efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Barbara Di Francesco, Daniela Verzella, Daria Capece, Davide Vecchiotti, Mauro Di Vito Nolfi, Irene Flati, Jessica Cornice, Monica Di Padova, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni
Summary: Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with a high need for new therapeutic options. Constitutive NF-kappa B activation has been reported in around 40% of AML patients, making targeting the NF-kappa B pathway an attractive strategy to treat AML.
Article
Medicine, Research & Experimental
Lin Zhang, Min Wu, Weikai Guo, Shuangshuang Zhu, Shen Li, Shiyi Lv, Yan Li, Layang Liu, Yajing Xing, Huang Chen, Mingyao Liu, Shihong Peng, Yihua Chen, Zhengfang Yi
Summary: BCL6 is a transcriptional repressor that plays a role in immune cell differentiation, DNA damage repair, cell cycle, and apoptosis. A small molecule compound called WK499 has been identified as a inhibitor of BCL6, which inhibits the proliferation of AML cells and enhances the sensitivity of AML to chemotherapy. WK499 achieves this by disrupting the interactions between BCL6 and its corepressor proteins, leading to changes in downstream genes and induction of cell cycle arrest and apoptosis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Engineering, Multidisciplinary
Meira Yisraeli Salman, Jacob M. Rowe, Nir Weigert
Summary: The modern therapy of acute myeloid leukemia (AML) has evolved significantly over the years through advancements in combination chemotherapy, reliable cytogenetics, unique mutational profiling, and the understanding of tumor burden. These advances have paved the way for personalized medicine in AML, leading to targeted agents that have revolutionized treatment outcomes by reducing toxicity and improving efficacy. The focus of this review is on FLT3 inhibitors as a well-studied targeted agent in AML, demonstrating the impact on prognostication and therapeutics, as well as the potential for other promising targeted agents in development.
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)