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
Oncology
Khashayar Ahmadmehrabi, Ali R. Haque, Ahmed Aleem, Elizabeth A. Griffiths, Gregory W. Roloff
Summary: Acute myeloid leukemia (AML) is a predominantly fatal blood cancer, and treatment options remained stagnant for forty years until recently multiple new agents were approved. These new therapies mainly function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival, and have been approved both as single agents and in combination with conventional chemotherapeutics.
Article
Immunology
Caitlin R. Rausch, Adam J. DiPippo, Ying Jiang, Courtney D. DiNardo, Tapan Kadia, Abhishek Maiti, Guillermo Montalban-Bravo, Farhad Ravandi, Dimitrios P. Kontoyiannis
Summary: The rate of breakthrough invasive fungal infections (bIFI) during remission induction chemotherapy was low (4%) in newly diagnosed AML patients receiving mold-active triazole antifungals for primary antifungal prophylaxis (PAP). Lower complete remission rate was observed in patients with bIFI. The rate of bIFI was comparable among different PAP agents and chemotherapy intensities.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Hematology
Sigrid S. Skanland, Anthony R. Mato
Summary: Insight into the mechanisms of resistance to targeted therapies in chronic lymphocytic leukemia (CLL) has led to the development of strategies to prevent and overcome resistance, including combination therapies targeting bypass mechanisms, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. These approaches aim to secure effective treatment options at the relapsed setting and overcome acquired resistance to existing therapies.
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: The origin cell of chronic myeloid leukemia is a hematopoietic stem cell and the hallmark oncogene is BCR-ABLp210, which influences hematopoietic stem and progenitor cells to myeloid fate. Studies have shown that BCR-ABLp210 affects the epigenome, leading to dysregulation of fate choice for hematopoietic stem cells, but the reason why neutrophils are abundantly produced in the disease remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Robert Szasz, Bela Telek, Arpad Illes
Summary: This study compared the impact of fitness on prolonged cytopenias and reported real-life data on FCR treatment. The findings show a decrease in the number of patients treated with FCR in recent years, likely due to the availability of targeted therapies.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
Article
Oncology
Bryann Pardieu, Justine Pasanisi, Frank Ling, Reinaldo Dal Bello, Justine Penneroux, Angela Su, Romane Joudinaud, Laureen Chat, Hsin Chieh Wu, Matthieu Duchmann, Gaetano Sodaro, Clementine Chauvel, Florence A. Castelli, Loic Vasseur, Kim Pacchiardi, Yannis Belloucif, Marie-Charlotte Laiguillon, Eshwar Meduri, Camille Vaganay, Gabriela Alexe, Jeannig Berrou, Chaima Benaksas, Antoine Forget, Thorsten Braun, Claude Gardin, Emmanuel Raffoux, Emmanuelle Clappier, Lionel Ades, Hugues de The, Francois Fenaille, Brian J. Huntly, Kimberly Stegmaier, Herve Dombret, Nina Fenouille, Camille Lobry, Alexandre Puissant, Raphael Itzykson
Summary: By analyzing multiple AML datasets, we identified SLC7A11 as a potential gene that is essential for AML cell survival. Inhibition of SLC7A11 using genetic and chemical methods reduced the viability and clonogenic capacity of AML cell lines. Sulfasalazine, a drug with xCT inhibitory activity, showed anti-leukemic effects against primary AML samples in vitro. Inhibition of xCT affected multiple metabolic pathways, leading to depletion of glutathione pools and oxidative stress-induced cell death in leukemic cells.
Review
Hematology
Shyam A. Patel, Mark R. Litzow, Jan Cerny
Summary: In recent years, FDA has approved multiple therapeutics for AML, but the role of maintenance therapy in AML is still relatively unrealized. Many clinical trials have demonstrated benefits of using various therapeutics in the maintenance setting for AML patients. Oral hypomethylating agent therapy has shown benefits in overall survival and disease-free survival in the maintenance setting for AML.
Review
Immunology
Sangeeta Goswami, Swetha Anandhan, Deblina Raychaudhuri, Padmanee Sharma
Summary: This study describes current therapies that aim to modulate the functional activities of myeloid cell populations in the tumor microenvironment, impacting their recruitment, survival, and activity. Myeloid cells are the most abundant immune components in the tumor microenvironment and have diverse functions. The authors highlight key features of monocyte and macrophage biology as potential targets for cancer therapies and discuss the need for a deeper understanding of myeloid cells to improve clinical outcomes.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Cell Biology
Angela Ianniciello, G. Vignir Helgason
Summary: Minimal residual disease (MRD) is the main cause of relapse in solid cancers and leukemias. In chronic myeloid leukemia (CML), autophagy plays a crucial role in maintaining the survival of drug resistant leukemic stem cells. Inhibition of autophagy-initiating kinase ULK1 could lead to stress-induced differentiation of leukemic stem cells, making them sensitive to drug treatment, providing a promising strategy for selective eradication of leukemic stem cells in CML patients.
Review
Hematology
Julian A. Waksal, Claudia Bruedigam, Rami S. Komrokji, Catriona H. M. Jamieson, John O. Mascarenhas
Summary: Human telomeres are repetitive sequences at the ends of chromosomes, playing important roles in preserving genomic integrity and preventing loss of genetic information. Telomerase, an enzyme involved in maintaining telomere length, is upregulated in malignant cells, making it a potential target for cancer therapy. This review focuses on the biology of telomeres and telomerase, and discusses the development of telomerase-targeted therapeutic candidates, particularly imetelstat, which has shown promising results in myeloid malignancies.
Review
Cell & Tissue Engineering
Hanieh Mojtahedi, Niloufar Yazdanpanah, Nima Rezaei
Summary: CML is driven by the BCR-ABL1 oncoprotein, and TKI therapy has been successful. However, mechanisms leading to resistance and disease progression in CML LSCs call for targeted therapies to eradicate them.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Oncology
Jiasheng Wang, Benjamin Tomlinson, Hillard M. Lazarus
Summary: The search for effective therapies for the highly heterogenous disease acute myeloid leukemia (AML) has been difficult. However, sophisticated molecular studies have identified defects within AML cells that can be targeted using small molecule agents, leading to the development of several FDA-approved medications. Additionally, emerging small molecules offer new treatment options for AML, and the combination of these agents with cytotoxic drugs and immunotherapy may further improve outcomes.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ryo Yoshimaru, Yosuke Minami
Summary: Tyrosine kinase inhibitors have been successful in treating chronic myeloid leukemia, but some patients do not respond to this therapy. Resistance to TKIs is mainly associated with mutations in the BCR::ABL1 kinase domain, but other mechanisms independent of BCR::ABL1 are also involved. Known cancer gene mutations and Philadelphia-associated rearrangements are two types of mechanisms that contribute to TKI resistance. Further studies are needed to analyze genetic information and guide risk-adapted therapy for a potential cure of CML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)