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)
Review
Oncology
David C. de Leeuw, Gert J. Ossenkoppele, Jeroen J. W. M. Janssen
Summary: The treatment of elderly patients with acute myeloid leukemia is a challenge due to patient diversity and disease heterogeneity. Determining fitness and selecting appropriate treatments based on factors like age, performance status, and comorbidities is important. Recent developments such as the addition of venetoclax, targeted therapy with IDH1/2 and FLT3 inhibitors, and improved formulations of existing drugs have improved treatment outcomes. Selecting patient-tailored treatments based on fitness and disease biology is essential.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Meghan Shekar, Gabriela Llaurador Caraballo, Jyotinder N. Punia, Choladda V. Curry, Kevin E. Fisher, Michele S. Redell
Summary: Activating mutations and fusions of the ALK oncogene have improved treatment outcomes for patients with malignancies. In this study, a rare finding of an activating ALK fusion in an adolescent patient with AML without monosomy 7 was reported. Crizotinib was added to the frontline therapy and was well tolerated. However, insurance coverage prevented post-HSCT use of crizotinib.
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
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
Genetics & Heredity
Julie Quessada, Wendy Cuccuini, Paul Saultier, Marie Loosveld, Christine J. Harrison, Marina Lafage-Pochitaloff
Summary: Pediatric acute myeloid leukemia is a rare and heterogeneous disease with improved treatment outcomes but high relapse rates. Cytogenetics play a crucial role in diagnosis and prognosis, with cytogenetic abnormalities in current therapeutic protocols guiding risk-adapted therapy.
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
Oncology
Bhavana Bhatnagar, Ramiro Garzon
Summary: MicroRNAs (miRs) play crucial roles in cellular processes such as differentiation, proliferation, and survival, and dysregulated miR expression is associated with various cancer types, including AML, where it can serve as a prognostic indicator. MiRs have potential as biomarkers and for guiding medical decisions, and preclinical studies provide strong rationale for developing novel therapeutic strategies targeting miRs in AML.
FRONTIERS IN ONCOLOGY
(2021)
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
Oncology
Ryan J. Stubbins, Annabel Francis, Florian Kuchenbauer, David Sanford
Summary: This article reviews the treatment and management strategies for acute myeloid leukemia (AML), focusing on individualized intensive therapy, recently approved novel therapies, and post-remission therapy selection. It also discusses the management of relapsed and refractory AML patients, targeted treatment, and allogeneic stem cell transplant. Non-intensive treatment for older and unfit patients, as well as the integration of palliative care in AML management, are also reviewed.
Review
Biochemistry & Molecular Biology
Fabio Andreozzi, Fulvio Massaro, Sebastian Wittnebel, Chloe Spilleboudt, Philippe Lewalle, Adriano Salaroli
Summary: For decades, intensive chemotherapy (IC) has been considered the best therapeutic option for treating acute myeloid leukemia (AML). Recently, several new drugs have emerged, providing new opportunities and challenges for the treatment of both fit and unfit AML patients. Access to and inclusion in clinical trials of these new drugs should be encouraged to define the future standard of treatment for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
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)
Article
Hematology
Justin M. Watts, Maria R. Baer, Jay Yang, Thomas Prebet, Sangmin Lee, Gary J. Schiller, Shira N. Dinner, Arnaud Pigneux, Pau Montesinos, Eunice S. Wang, Karen P. Seiter, Andrew H. Wei, Stephane De Botton, Montserrat Arnan, Will Donnellan, Anthony P. Schwarer, Christian Recher, Brian A. Jonas, P. Brent Ferrell Jr, Christophe Marzac, Patrick Kelly, Jennifer Sweeney, Sanjeev Forsyth, Sylvie M. Guichard, Julie Brevard, Patrick Henrick, Hesham Mohamed, Jorge E. Cortes
Summary: This study evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity of Olutasidenib in patients with acute myeloid leukemia or myelodysplastic syndrome with mutant IDH1. The results showed that Olutasidenib, as monotherapy or in combination with azacitidine, was well tolerated and exhibited meaningful clinical activity. These findings provide a rationale for further evaluation of Olutasidenib in different populations of patients with myeloid malignancies.
LANCET HAEMATOLOGY
(2023)
Article
Urology & Nephrology
Camilo Montero, Nancy Yomayusa, Rodolfo Torres, Jorge Cortes, Carlos Alvarez, Juan Gallo, Guillermo Aldana, Andres Acevedo, Maria Rios, Johana Echeverri, Zuly Yepes, Adriana Silva, Diana Gayon, Jorge Perez, Milciades Ibanez
Summary: This study aimed to evaluate asymptomatic CMV reactivation and CMV disease in kidney transplant recipients with positive CMV serostatus. The results showed that asymptomatic CMV reactivation was higher in patients who received thymoglobulin induction, while the rates of CMV disease were similar between the two treatment groups. The significant difference in asymptomatic CMV reactivation between the two groups did not affect graft function and histology.
Article
Oncology
Nikhil Shri Sahajpal, Ashis K. Mondal, Harmanpreet Singh, Ashutosh Vashisht, Sudha Ananth, Daniel Saul, Alex R. Hastie, Benjamin Hilton, Barbara R. DuPont, Natasha M. Savage, Vamsi Kota, Alka Chaubey, Jorge E. Cortes, Ravindra Kolhe
Summary: The current genetic testing of myeloid cancers lacks resolution and is limited to specific genomic regions/genes. This study used a combination of high-resolution cytogenetic technology and next-generation sequencing to obtain a comprehensive genomic profile of these tumors. The combinatorial approach identified new genetic alterations and clinically relevant alterations in previously negative cases.
Article
Hematology
Mycal Casey, Lorriane Odhiambo, Nidhi Aggarwal, Mahran Shoukier, K. M. Islam, Jorge Cortes
Summary: Despite advances in cancer outcomes, there are significant health disparities in the treatment of lymphomas. This study examined the representation of different demographic groups in randomized controlled trials (RCTs) for lymphoma and found significant underrepresentation of black, Hispanic, and female patients. Geographic distribution of trials also limited access for patients in certain areas. Correcting enrollment disparities is crucial to ensure that the results of these trials are applicable to all populations.
Article
Oncology
Fabio Efficace, Francesco Cottone, Betina Yanez, Vamsi Kota, Fausto Castagnetti, Giovanni Caocci, Massimiliano Bonifacio, Andrea Patriarca, Isabella Capodanno, Maria Cristina Miggiano, Mario Tiribelli, Massimo Breccia, Luigia Luciano, Valentina Giai, Alessandra Iurlo, Elisabetta Abruzzese, Carmen Fava, Shira Dinner, Jessica K. Altman, Gianantonio Rosti, Jorge Cortes, Marco Vignetti, David Cella
Summary: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates. The current findings suggest that systematic monitoring of patient-reported symptoms is associated with high adherence rates.
Article
Oncology
Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C. Issa, Sherry A. Pierce, Kelly A. Soltysiak, Martha S. Tingen, Jorge E. Cortes
Summary: This study investigated the impact of geographic disparities on cancer survival. The study found that factors such as age, income, race, and distance to cancer centers were predictive of survival. The results showed significant disparities in cancer care based on geographic locations.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Economics
Jorge E. Cortes, Delphine Rea, Michael J. Mauro, Diana Tran, Pearl Wang, Kejal Jadhav, Aurore Yocolly, Koji Sasaki
Summary: This study assessed and compared the health care resource utilization (HCRU) rates of asciminib and bosutinib among 3 L+ patients with chronic myeloid leukemia in chronic phase (CML-CP) in the ASCEMBL trial. The results showed that asciminib-treated patients had lower resource utilization compared to bosutinib-treated patients over the long-term.
JOURNAL OF MEDICAL ECONOMICS
(2023)
Review
Hematology
Marisol Miranda-Galvis, Kellen C. Tjioe, E. Andrew Balas, Gagan Agrawal, Jorge E. Cortes
Summary: This article evaluates the impact of social determinants of health on the outcomes of patients with hematologic malignancies. The study found that factors such as education level, health insurance coverage, income level, and marital status significantly affect patients' survival rates. However, there are contradictory reports regarding the effect of distance to treatment centers on treatment outcomes. Additionally, data on transportation, debt, diet, and other factors are lacking.
Review
Hematology
Mahesh Swaminathan, Jorge E. E. Cortes
Summary: Gemtuzumab-ozogamicin (GO) is an ADC approved for the treatment of CD33(+) AML. Despite initial recall due to lack of efficacy and hepatotoxicities, subsequent phase 3 studies showed significant survival benefits with lower and fractionated doses of GO in combination with standard chemotherapy. GO at a dose of 6 mg/m(2) was associated with higher grade > 3 hepatotoxicities and VOD compared to 3 mg/m(2). GO has been reapproved in 2017 and is currently being studied for its role in combination therapies and MRD elimination in CD33(+) AML patients.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Hematology
Gemma Shay, Michael W. Deininger, Tim H. Bruemmendorf, Jeffrey H. Lipton, Leif Stenke, Eric Leip, Simon Purcell, Andrea Viqueira, Jorge E. Cortes
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Meeting Abstract
Oncology
Jane Apperley, Jorge Cortes, Elias Jabbour, Andreas Hochhaus, Timothy Hughes, Charles Chuah, Hugues de Lavallade, Michael Deininger, Jeffrey H. Lipton, Elza Lomaia, Lori Maness, Michael Mauro, James McCloskey, Beatriz Moiraghi, Carolina Pavlovsky, Christine Rojas, Philippe Rousselot, Tomasz Sacha, Moshe Talpaz, Anna Turkina, Maria Undurraga Sutton, Xiaowei Ren, Alexander Vorog, Gianantonio Rosti
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Ehab Atallah, Michael Mauro, Koji Sasaki, Moshe Levy, Paul Koller, Daisy Yang, Dramane Laine, John Sabo, Ennan Gu, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Aram Bidikian, Sreyashi Basu, Zhong He, Himachandana Atluri, Jabra Zarka, Michael Andreeff, Koji Sasaki, Elias Jabbour, Jorge E. Cortes, Padmanee Sharma, Ghayas C. Issa
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Joannie Clements, Cristina Ruiz, Andrea Damon, Peter Schuld, Pauline Frank, Cristina Constantinescu, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Jorge Cortes, Michael Deininger, Elza Lomaia, Beatriz Moiraghi, Maria Undurraga Sutton, Carolina Pavlovsky, Charles Chuah, Tomasz Sacha, Jeffrey H. Lipton, James McCloskey, Philippe Rousselot, Gianantonio Rosti, Hugues de Lavallade, Christine Rojas, Anna Turkina, Moshe Talpaz, Michael Mauro, Vickie Lu, Alexander Vorog, Jane Apperley
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
