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.
Article
Medicine, Research & Experimental
Na Man, Gloria Mas, Daniel L. Karl, Jun Sun, Fan Liu, Qin Yang, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Ye Xu, Stephanie Duffort, Pierre-Jacques Hamard, Chuan Chen, Beth E. Zucconi, Luisa Cimmino, Feng-Chun Yang, Mingjiang Xu, Philip A. Cole, Maria E. Figueroa, Stephen D. Nimer
Summary: This study identified a tumor suppressor role of the acetyltransferase p300 in MDS, with loss of p300 enhancing HSPC proliferation and self-renewal, ultimately increasing leukemogenicity. Mechanistically, loss of p300 altered gene expression and promoted leukemia development, while activating p300 activity countered these effects. This suggests a potential therapeutic application of p300 activators in treating MDS with TET2 mutations.
Review
Biochemistry & Molecular Biology
Thomas Cluzeau, Michael Loschi, Pierre Fenaux, Rami Komrokji, David A. Sallman
Summary: This article reviews the progress in targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, focusing on the use of active agents and future treatment directions. It emphasizes the importance of understanding the clinical characteristics of the disease and the impact of TP53 mutant burden on patient clinical trajectory.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Review
Oncology
Michael Loschi, Pierre Fenaux, Thomas Cluzeau
Summary: TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by poor prognosis. In this review, we analyze the prognosis of these diseases, focusing on the extent of TP53 mutation status and its correlation with cytogenetic complexity. We discuss the potential improvement in outcome based on recent results obtained with new drugs (especially eprenetapopt and magrolimab). The impact of allogeneic hematopoietic stem cell transplantation (aHSCT) and post-transplantation treatment is also emphasized.
Review
Medicine, General & Internal
Petter S. Woll, Tetsuichi Yoshizato, Eva Hellstrom-Lindberg, Thoas Fioretos, Benjamin L. Ebert, Sten Eirik W. Jacobsen
Summary: The genetic architecture of cancer has been extensively studied, leading to the identification of new therapeutic targets and the development of promising treatment strategies. However, disease progression, relapse, and treatment-related mortality remain challenging in certain types of cancer such as myelodysplastic syndromes and acute myeloid leukemia. The persistence of rare leukemic stem cells following therapy underscores the resistance mechanisms of these cells and their role in relapse. To improve treatment strategies, there is a need to better understand and characterize the stem cells associated with these diseases at the cellular, molecular, and genetic levels.
JOURNAL OF INTERNAL MEDICINE
(2022)
Review
Oncology
Kah Keng Wong, Rosline Hassan, Nik Soriani Yaacob
Summary: Decitabine and guadecitabine are hypomethylating agents that enhance anti-tumor immunity in AML and MDS patients by upregulating cancer/testis antigens, stimulating T cells, and inducing immune checkpoint molecules expression. Combining these agents with cancer vaccines or immune checkpoint blockade therapy shows promising efficacy in treating relapsed/refractory AML and high-risk MDS cases.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Vlad Andrei Cianga, Lydia Campos Catafal, Petru Cianga, Mariana Pavel Tanasa, Mohamad Cherry, Phillipe Collet, Emmanuelle Tavernier, Denis Guyotat, Cristina Rusu, Carmen Mariana Aanei
Summary: The study investigated NK cell maturation in bone marrow under different conditions and found impaired NK cell antitumor response and phenotypic shift in MDS and AML settings. The results suggest immune response failure during myeloid malignancy pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Yang Mei, Kehan Ren, Yijie Liu, Annabel Ma, Zongjun Xia, Xu Han, Ermin Li, Hamza Tariq, Haiyan Bao, Xinshu Xie, Cheng Zou, Dingxiao Zhang, Zhaofeng Li, Lili Dong, Amit Verma, Xinyan Lu, Yasmin Abaza, Jessica K. Altman, Madina Sukhanova, Jing Yang, Peng Ji
Summary: This study reveals that age-related MDS can transform into AML, and the cytokine IL-6 plays a significant role in this transformation. By studying a double knockout mouse model and high-risk MDS patients, blocking IL-6 signaling was found to significantly ameliorate AML progression, indicating the clinical significance of targeting IL-6 signaling in treating high-risk MDS.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
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
Hematology
Harrison K. Tsai, Christopher J. Gibson, H. Moses Murdock, Phani Davineni, Marian H. Harris, Eunice S. Wang, Lukasz P. Gondek, Annette S. Kim, Valentina Nardi, R. Coleman Lindsley
Summary: The study reveals the presence of complex secondary events in patients with KMT2A-PTD, which may be related to the occurrence and relapse of acute myeloid leukemia and myelodysplastic syndrome.
Review
Oncology
Romane Joudinaud, Thomas Boyer
Summary: MDS and AML transformation is supported by alterations affecting malignant stem cells, including metabolic, phenotypic, and genetic characteristics. MDS-SCs are more likely derived from healthy HSCs, while LSCs may originate from healthy progenitors like LMPP. Overexpression of CD123 and CLL1 markers is seen in high risk-MDS, leading to exciting therapeutic applications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Sayantanee Dutta, Jennifer Moritz, Gudrun Pregartner, Gerhard G. Thallinger, Ilona Brandstaetter, Karin Lind, Simin Rezania, Freya Lyssy, Andreas Reinisch, Armin Zebisch, Andrea Berghold, Albert Woelfler, Heinz Sill
Summary: The study found TP53 aberrations to be common in AML and MDS patients, with similar clinical and cytogenetic characteristics, but higher overall survival in MDS patients compared to AML patients. High transformation rate of TP53 aberrant MDS reduces survival probability for patients.
ANNALS OF HEMATOLOGY
(2022)
Review
Oncology
Xingcheng Yang, Ling Ma, Xiaoying Zhang, Liang Huang, Jia Wei
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases that arise from the bone marrow. Dysregulated immune microenvironment, including the molecules PD-1 and PD-L1, play important roles in the pathogenesis of MDS and AML. However, clinical trials using PD-1/PD-L1 inhibitors have reported mixed responses in patients with these diseases.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Pathology
Pimjai Niparuck, Pornnapa Police, Phichchapha Noikongdee, Kanchana Siriputtanapong, Nittaya Limsuwanachot, Budsaba Rerkamnuaychoke, Suporn Chuncharunee, Teerapong Siriboonpiputtana
Summary: The prevalence of TP53 mutation in de novo AML and MDS-EB patients in Asian population was low but had impact on survival. Patients with monosomy or complex karyotype were more likely to have TP53 mutation.
DIAGNOSTIC PATHOLOGY
(2021)
Review
Oncology
Matthew Ku, Meaghan Wall, Ruth N. MacKinnon, Carl R. Walkley, Louise E. Purton, Constantine Tam, David Izon, Lynda Campbell, Heung-Chin Cheng, Harshal Nandurkar
LEUKEMIA & LYMPHOMA
(2015)
Article
Cell Biology
Ruth N. MacKinnon, Hendrika M. Duivenvoorden, Lynda J. Campbell, Meaghan Wall
CYTOGENETIC AND GENOME RESEARCH
(2016)
Article
Genetics & Heredity
Thian T. Beh, Ruth N. MacKinnon, Paul Kalitsis
MOLECULAR CYTOGENETICS
(2016)
Article
Oncology
Anuratha Sakthianandeswaren, Marie J. Parsons, Dmitri Mouradov, Ruth N. MacKinnon, Bruno Catimel, Sheng Liu, Michelle Palmieri, Christopher Love, Robert N. Jorissen, Shan Li, Lachlan Whitehead, Tracy L. Putoczki, Adele Preaudet, Cary Tsui, Cameron J. Nowell, Robyn L. Ward, Nicholas J. Hawkins, Jayesh Desai, Peter Gibbs, Matthias Ernst, Ian Street, Michael Buchert, Oliver M. Sieber
Article
Oncology
Ruth N. MacKinnon, Carly Selan, Meaghan Wall, Elizabeth Baker, Harshal Nandurkar, Lynda J. Campbell
GENES CHROMOSOMES & CANCER
(2010)
Letter
Oncology
Loi-Khim Chin, Chan Y. Cheah, Patricia M. Michael, Ruth N. MacKinnon, Lynda J. Campbell
LEUKEMIA & LYMPHOMA
(2012)
Article
Oncology
Ruth N. MacKinnon, Hendrika M. Duivenvoorden, Lynda J. Campbell
Article
Oncology
Ruth N. MacKinnon, George Kannourakis, Meaghan Wall, Lynda J. Campbell
Article
Oncology
Ruth N. MacKinnon, Lynda J. Campbell
Article
Genetics & Heredity
Ruth N. MacKinnon, Carly Selan, Adrian Zordan, Meaghan Wall, Harshal Nandurkar, Lynda J. Campbell
MOLECULAR CYTOGENETICS
(2012)
Article
Multidisciplinary Sciences
Matthew Ku, Ruth N. MacKinnon, Meaghan Wall, Nisha Narayan, Carl Walkley, Heung-Chin Cheng, Lynda J. Campbell, Louise E. Purton, Harshal Nandurkar
SCIENTIFIC REPORTS
(2019)
Article
Genetics & Heredity
Ruth N. MacKinnon, Joanne Peverall, Lynda J. Campbell, Meaghan Wall
MOLECULAR CYTOGENETICS
(2020)
Review
Biochemistry & Molecular Biology
Ruth N. MacKinnon, Lynda J. Campbell
GENETICS RESEARCH INTERNATIONAL
(2011)
Article
Oncology
Ruth N. MacKinnon, Cris Patsouris, Ilse Chudoba, Lynda J. Campbell
GENES CHROMOSOMES & CANCER
(2007)
