Review
Oncology
Rahul S. S. Bhansali, Keith W. W. Pratz, Catherine Lai
Summary: Acute myeloid leukemia (AML), the most common acute leukemia in adults, has seen significant advancements in understanding its molecular profile and treatment options in the past decade. The classification of AML subtypes has shifted from morphology to molecular and genetic basis, leading to improved outcomes with low-intensity induction therapy and targeted oral therapies. However, challenges remain in sequencing and combining therapies, as well as addressing poor prognosis in certain subtypes like TP53 mutations. This review discusses recent updates in AML classification, low-intensity and novel oral combination therapies, and ongoing translational advances for high-risk disease subtypes.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(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
Pharmacology & Pharmacy
Natasa Tosic, Irena Marjanovic, Jelena Lazic
Summary: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that accounts for 20% of pediatric leukemia cases. While overall survival rates have improved, AML remains a leading cause of mortality in pediatric cancers. Targeted therapy approaches and advances in genomic techniques have identified novel therapeutic targets and provided potential for significant clinical benefits in pediatric AML.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tulasigeri M. M. Totiger, Anirban Ghoshal, Jenna Zabroski, Anya Sondhi, Saanvi Bucha, Jacob Jahn, Yangbo Feng, Justin Taylor
Summary: Therapeutic developments for acute myeloid leukemia (AML) have been ongoing for fifty years, resulting in multiple approved targeted therapies. However, there is still a need for molecular treatments that can provide long-term remissions and cure for this heterogeneous disease. The development of small molecule drugs targeting sub-types of AML has been hindered by drug resistance, but combination therapies like venetoclax and azacitidine have shown improved response rates compared to chemotherapy. Despite the complexity of AML, there is a demand for therapies that target specific abnormalities and eliminate leukemia-initiating cells.
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.
Review
Pediatrics
Huan Xu, Yuxi Wen, Runming Jin, Hongbo Chen
Summary: This review discusses the genetic alterations and epigenetic dysregulations of hematopoietic progenitor cells in acute myeloid leukemia (AML), emphasizing the role of epigenetic abnormalities in leukemogenesis. The current progress in epigenetic targeted therapy and its potential value in precision and combinational therapy for pediatric AML are also described.
FRONTIERS IN PEDIATRICS
(2022)
Article
Immunology
Ewa Kubicka, Lawrence G. Lum, Manley Huang, Archana Thakur
Summary: The study demonstrates that arming activated T cells (ATCs) with bispecific antibodies (BiAbs) can effectively target and lyse acute myeloid leukemia (AML) cells and leukemic stem cells (LSCs), providing a potent and non-toxic therapeutic strategy to enhance chemo-responsiveness in older patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Hematology
Shannon R. McCurdy, Selina M. Luger
Summary: Recent advances in AML therapy have shifted towards the use of novel targeted agents alongside traditional intense chemotherapy, providing remission options for patients who may not be suitable for cytotoxic treatments. These new approaches include combination therapies with hypomethylating agents and venetoclax, as well as the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy for specific AML subtypes. More research is needed to improve outcomes for high-risk subgroups.
Review
Biochemistry & Molecular Biology
Hironori Arai, Yosuke Minami, SungGi Chi, Yoshikazu Utsu, Shinichi Masuda, Nobuyuki Aotsuka
Summary: Comprehensive genomic profiling examinations have led to the development of new molecular-targetable therapies across solid tumors, while elucidation of hereditary tumors has paved the way for new treatments and management strategies. In the context of AML, there is a lack of focus on tumor-agnostic or hereditary mutations and associated molecular-targeted therapies. Studies on tumor-agnostic mutations in AML are exploring the potential for targeted therapies.
Review
Biochemistry & Molecular Biology
Piotr Obszanski, Anna Kozlowska, Jakub Wancowiat, Julia Twardowska, Monika Lejman, Joanna Zawitkowska
Summary: Acute myeloid leukemia (AML) comprises 15-20% of childhood leukemia cases, with a survival rate of not exceeding 82% and 5-year event-free survival rates ranging from 46% to 69%. The disease is influenced by multiple mutations and epigenetic changes, affecting treatment susceptibility and relapse rate. Molecular-targeted therapies have been developed and studied in clinical trials to address these challenges, originally introduced in adult AML and now gradually changing the therapeutic approach to pediatric AML. Research involving larger pediatric populations is needed to further improve outcomes.
Review
Biochemistry & Molecular Biology
Marco Gallazzi, Maghalie Anais Marie Ucciero, Danilo Giuseppe Faraci, Abdurraouf Mokhtar Mahmoud, Wael Al Essa, Gianluca Gaidano, Samir Mouhssine, Elena Crisa
Summary: Immunotherapy targeting CD47, immune checkpoints, and TLR2 shows promise in the treatment of AML and MDS. Novel monoclonal antibodies targeting CD33, CD123, CD45, and CD70 are also being investigated. These therapies have different mechanisms of action and can be used alone or in combination with other drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Nicole Baeumer, Annika Scheller, Lisa Wittmann, Andreas Faust, Mara Apel, Subbaiah Chary Nimmagadda, Christiane Geyer, Katharina Grunert, Neele Kellmann, Matthias Peipp, Sareetha Kailayangiri, Matias Ezequiel Gutierrez Suburu, Cristian A. Strassert, Mathias Schenk, Lilo Greune, Christian Rueter, Petra Dersch, Wolfgang Hartmann, Claudia Rossig, Dario Neri, Carsten Mueller-Tidow, Christian Schwoeppe, Christoph Schliemann, Cyrus Khandanpour, Georg Lenz, Wolfgang E. Berdel, Sebastian Baeumer
Summary: This study developed a new experimental platform technology for targeting molecular oncogenes in AML using electrostatic nanocarriers. It showed therapeutic activity against AML in cell lines and animal models, specifically targeting mutated genes.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sung-Gi Chi, Yosuke Minami
Summary: This article summarizes the recent updates on molecular targeting agents and emerging gene-specific strategies. FLT3 and IDH inhibitors are being tested together with conventional chemotherapy in patients who are fit for treatment and those who are not eligible for intensive therapy. Other potential therapeutic strategies include targeting the menin-MLL complex pathway, downstream signaling molecule SYK, and developing next-generation p53 stabilizers. The TP53 mutation remains a challenge, but promising results have been observed with the anti-CD47 antibody magrolimab in combination with azacitidine in patients carrying the TP53 mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)