Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Article
Oncology
Jingmei Yang, Ran Friedman
Summary: This study suggests that a multi-targeted intervention involving a CDK4/6 inhibitor with a FLT3 inhibitor or a pan-PI3K inhibitor might be a valuable therapeutic strategy for AML to overcome drug resistance.
CANCER CELL INTERNATIONAL
(2023)
Review
Chemistry, Medicinal
Vincent G. Sorrentino, Srijan Thota, Edward A. Gonzalez, Pranela Rameshwar, Victor T. Chang, Jean-Pierre Etchegaray
Summary: Myelodysplastic Syndromes (MDS) affecting the elderly can progress to Acute Myeloid Leukemia (AML), with epigenetic alterations such as DNA methylation and chromatin modification playing a role in their initiation and progression. DNA hypomethylating agents like decitabine and azacitidine have shown efficacy in treating hematological malignancies, while the proteasome inhibitor bortezomib is used in multiple myeloma (MM) chemotherapy. Phase III clinical trials have demonstrated the potential of these drugs in prolonging survival and treating MDS and AML, although further research is needed to fully understand their mechanisms and effects.
Article
Multidisciplinary Sciences
Mohieddin Jafari, Mehdi Mirzaie, Jie Bao, Farnaz Barneh, Shuyu Zheng, Johanna Eriksson, Caroline A. Heckman, Jing Tang
Summary: This study proposes a bipartite network modelling approach to identify effective drug combinations for the treatment of acute myeloid leukaemia. By analyzing patient and cell line drug screening data, the authors discover multi-targeted drug combinations and validate their potency and synergy through in vitro experiments.
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Charlotte F. M. Hughes, Paolo Gallipoli, Rishu Agarwal
Summary: NGS technology plays a vital role in the understanding and management of myeloid malignancies such as AML and MDS. However, there are technical and biological challenges in the design, analysis, and interpretation of NGS results, highlighting the importance of expert guidance.
Article
Oncology
Lu Wang, Qi Zhang, Li Ye, Xingnong Ye, Wenli Yang, Hua Zhang, Xinping Zhou, Yanling Ren, Liya Ma, Xiang Zhang, Chen Mei, Gaixiang Xu, Kongfei Li, Yingwan Luo, Lingxu Jiang, Peipei Lin, Shuanghong Zhu, Wei Lang, Yuxia Wang, Chuying Shen, Yueyuan Han, Xiaozhen Liu, Haiyang Yang, Chenxi Lu, Jie Sun, Jie Jin, Hongyan Tong
Summary: Combining all-trans retinoic acid (ATRA) with decitabine (DAC) can improve the treatment outcomes of patients with higher-risk myelodysplastic syndromes (HR-MDS) and elderly acute myeloid leukaemia (AML) by inhibiting Nrf2 activation and antioxidative response induced by DAC, leading to ROS accumulation and cytotoxicity.
BRITISH JOURNAL OF CANCER
(2023)
Review
Pharmacology & Pharmacy
Jiale Ma, Zheng Ge
Summary: A systematic review and network meta-analysis compared the efficacy and safety of DAC and AZA in AML and HR-MDS patients. Both DAC and AZA showed better overall response rate and longer overall survival compared to CCR, but DAC demonstrated higher efficacy in achieving complete remission rate compared to AZA.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Xiwen Tong, Mengyuan Li, Jie Jin, Yi Li, Li Li, Yizhou Peng, Lifang Huang, Bin Xu, Fankai Meng, Xia Mao, Liang Huang, Wei Huang, Donghua Zhang
Summary: This study aimed to analyze the risk factors associated with relapse post allo-HSCT in R/R AML and high-risk MDS patients and evaluate the efficacy of a new conditioning regimen containing decitabine and cladribine. The results showed that CR before allo-HSCT and matched sibling donors were independent protective factors for survival, while DNMT3A abnormality was an independent risk factor for both relapse and no-relapse survival. The new conditioning regimen demonstrated a low relapse rate, high survival rate, and no increased incidence of GVHD or adverse effects, suggesting its potential use in allo-HSCT for R/R AML and high-risk MDS.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Pharmacology & Pharmacy
Heather A. Ogana, Samantha Hurwitz, Nathan Wei, Eliana Lee, Kayla Morris, Karina Parikh, Yong-Mi Kim
Summary: Acute myeloid leukaemia (AML) has a poor prognosis and new therapeutic strategies are needed. The bone marrow (BM) microenvironment contains niches that interact with both normal haematopoietic stem cells and AML cells. Integrins, which are adhesion molecules in the BM microenvironment, play a central role in AML. AML cells express integrins that bind to ligands in the microenvironment, leading to adhesion, intracellular signalling, and drug resistance. Targeting integrins in AML to disrupt interactions with the microenvironment is being explored as a strategy to overcome drug resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
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
Miriam Saiz-Rodriguez, Jorge Labrador, Beatriz Cuevas, David Martinez-Cuadron, Veronica Campuzano, Raquel Alcaraz, Isabel Cano, Miguel A. Sanz, Pau Montesinos
Summary: Azacitidine and decitabine are increasingly used for the treatment of older patients with acute myeloid leukaemia. A study comparing the efficacy of the two drugs found no significant differences in 1-year mortality and overall survival, as well as between different treatment schedules of decitabine. However, a shorter 5-day azacitidine regimen showed worse outcomes compared to the standard 7-day schedule. Further research is needed to explore combination schedules for future trials.
Review
Hematology
Sabine Kayser, Mark J. Levis
Summary: Research on the pathogenic mechanisms of AML has made remarkable advances in recent years, especially in the importance of cytogenetic and molecular aberrations. The development of new compounds targeting AML at a molecular level, based on increased understanding of AML pathogenesis facilitated by next-generation sequencing, has turned many hopeful predictions into therapeutic realities.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Lynn Chin, Chantelle Ye Gwen Wong, Harinder Gill
Summary: Mutations in the NPM1 gene are commonly found in AML patients, and this review explores various molecular methods for monitoring minimal residual disease (MRD) in NPM1-mutated AML. It also discusses current and potential drug therapies, as well as targeted strategies for aberrant NPM1 pathways and epigenetic regulation. The effects of stress on AML presentation and the advancement of immunotherapy are also mentioned.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Hematology
Luca Castagna, Katia Patti, Antonino Mule
Summary: Transplantation from haploidentical donors is commonly used, and cord blood reduction is considered as an alternative donor. Matsuda and colleagues' study suggests that cord blood is still a feasible option for allogeneic transplantation in advanced acute myeloid leukemia.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Justin Loke, Vinit Upasani, Charlotte Gaskell, Sonia Fox, Rachel Fletcher, Catherine Thomas, Louise Hopkins, Anita Kumari, Tina Tang, Emily Yafai, Rebecca Boucher, Victoria Homer, Arpad Toth, Y. L. Tracey Chan, Katie Randall, Tom Rider, Jenny O'Nions, Victoria Drew, Arvind Pillai, Moez Dungarwalla, Duncan Murray, Anjum Khan, Farooq Wandroo, Sally Moore, Pramila Krishnamurthy, Ya-Wen Jessica Huang, Steve Knapper, Jenny Byrne, Rui Zhao, Charles Craddock, Helen Parry, Paul Moss, Simon J. Stanworth, David M. Lowe
Summary: Limited data exist on the efficacy of COVID-19 vaccination in patients with AML/MDS-EB2. A prospective study found detectable antibodies against SARS-COV-2 spike antigen in all post-vaccine samples. T-cell reactivity to SARS-COV-2 spike protein was only seen in a subset of patients, and disease response and age were predictors of poor T-cell response.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Noel J. -M. Raynal, Elodie M. Da Costa, Justin T. Lee, Vazganush Gharibyan, Saira Ahmed, Hanghang Zhang, Takahiro Sato, Gabriel G. Malouf, Jean-Pierre J. Issa
MOLECULAR CANCER THERAPEUTICS
(2017)
Review
Oncology
Zdenko Herceg, Akram Ghantous, Christopher P. Wild, Athena Sklias, Lavinia Casati, Susan J. Duthie, Rebecca Fry, Jean-Pierre Issa, Richard Kellermayer, Igor Koturbash, Yukata Kondo, Johanna Lepeule, Sheila C. S. Lima, Carmen J. Marsit, Vardhman Rakyan, Richard Saffery, Jack A. Taylor, Andrew E. Teschendorff, Toshikazu Ushijima, Paolo Vineis, Cheryl Lyn Walker, Robert A. Waterland, Joe Wiemels, Srikant Ambatipudi, Davide Degli Esposti, Hector Hernandez-Vargas
INTERNATIONAL JOURNAL OF CANCER
(2018)
Article
Oncology
Hagop M. Kantarjian, Gail J. Roboz, Patricia L. Kropf, Karen W. L. Yee, Casey L. O'Connell, Raoul Tibes, Katherine J. Walsh, Nikolai A. Podoltsev, Elizabeth A. Griffiths, Elias Jabbour, Guillermo Garcia-Manero, David Rizzieri, Wendy Stock, Michael R. Savona, Todd L. Rosenblat, Jesus G. Berdeja, Farhad Ravandi, Edwin P. Rock, Yong Hao, Mohammad Azab, Jean-Pierre J. Issa
Article
Oncology
A. D. Kelly, H. Kroeger, J. Yamazaki, R. Taby, F. Neumann, S. Yu, J. T. Lee, B. Patel, Y. Li, R. He, S. Liang, Y. Lu, M. Cesaroni, S. A. Pierce, S. M. Kornblau, C. E. Bueso-Ramos, F. Ravandi, H. M. Kantarjian, J. Jelinek, J-P J. Issa
Article
Biochemistry & Molecular Biology
Charly R. Good, Jozef Madzo, Bela Patel, Shinji Maegawa, Nora Engel, Jaroslav Jelinek, Jean-Pierre J. Issa
NUCLEIC ACIDS RESEARCH
(2017)
Article
Multidisciplinary Sciences
Shan He, Yongnian Liu, Lijun Meng, Hongxing Sun, Ying Wang, Yun Ji, Janaki Purushe, Pan Chen, Changhong Li, Jozef Madzo, Jean-Pierre Issa, Jonathan Soboloff, Ran Reshef, Bethany Moore, Luca Gattinoni, Yi Zhang
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Jianfeng Xu, Jiejun Shi, Xiaodong Cui, Ya Cui, Jingyi Jessica Li, Ajay Goel, Xi Chen, Jean-Pierre Issa, Jianzhong Su, Wei Li
Summary: CHALM, a methylation quantification method that considers cell heterogeneity, enables detection of differentially methylated genes with distinct biological functions.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Oncology
Jean-Pierre Issa
Summary: The landmark paper by Kane and colleagues reported the association between DNA methylation in the promoter of the MLH1 gene and MMR deficiency in sporadic colon cancers. They showed that methylation in the promoter region resulted in loss of MLH1 protein expression and provided evidence for the two-hit hypothesis of tumor suppressor gene loss in cancer, incorporating both genetic and epigenetic mechanisms. This contribution helped to normalize the hypothesis of an epigenetic basis for cancer development.
Article
Oncology
Somnath Pandey, Rahinatou Djibo, Anais Darracq, Gennaro Calendo, Hanghang Zhang, Ryan A. Henry, Andrew J. Andrews, Stephen B. Baylin, Jozef Madzo, Rafael Najmanovich, Jean-Pierre J. Issa, Noel J-M Raynal
Summary: By combining drug screens, transcriptomic studies, and in vitro assays, our study identified toyocamycin as a potent and selective CDK9 inhibitor. Toyocamycin exhibits specific CDK9 inhibition in cancer cells and has the potential for cancer chemotherapy.
Article
Biotechnology & Applied Microbiology
Himani Vaidya, Hye Seon Jeong, Kelsey Keith, Shinji Maegawa, Gennaro Calendo, Jozef Madzo, Jaroslav Jelinek, Jean-Pierre J. Issa
Summary: DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. These findings have implications for tissue-specific functional declines with aging and the development of DNA-methylation-based biological clocks.
Review
Oncology
Rachael J. Werner, Andrew D. Kelly, Jean-Pierre J. Issa
Meeting Abstract
Oncology
Jean-Pierre Issa
Article
Oncology
Reka Toth, Dominique Scherer, Linda E. Kelemen, Angela Risch, Aditi Hazra, Yesilda Balavarca, Jean-Pierre J. Issa, Victor Moreno, Rosalind A. Eeles, Shuji Ogino, Xifeng Wu, Yuanqing Ye, Rayjean J. Hung, Ellen L. Goode, Cornelia M. Ulrich
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2017)
Review
Cell Biology
Andrew D. Kelly, Jean-Pierre J. Issa
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2017)
Article
Oncology
Gail J. Roboz, Hagop M. Kantarjian, Karen W. L. Yee, Patricia L. Kropf, Casey L. O'Connell, Elizabeth A. Griffiths, Wendy Stock, Naval G. Daver, Elias Jabbour, Ellen K. Ritchie, Katherine J. Walsh, David Rizzieri, Scott D. Lunin, Tania Curio, Woonbok Chung, Yong Hao, James N. Lowder, Mohammad Azab, Jean-Pierre J. Issa