Article
Cell Biology
Ana Cristina Vargas, Nima M. Ardakani, Daniel D. Wong, Fiona M. Maclean, Joseph Kattampallil, Richard Boyle, Leonardo Santos, Anthony J. Gill
Summary: NTRK-rearranged sarcomas are a heterogeneous group of tumors with either relatively simple or complex karyotypes. Chromosomal copy number variations involve multiple chromosomes, with complex karyotypes associated with more aggressive clinical behavior. Gains at chromosome 6p and 1q were the most common recurrent genetic alterations.
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
Biochemistry & Molecular Biology
Claudia Banescu, Florin Tripon, Carmen Muntean
Summary: Myelodysplastic neoplasm (MDS) is a diverse group of myeloid disorders that arise from hematopoietic stem cells and can progress to clonal hematopoiesis. MDS is characterized by an increased risk of transforming into acute myeloid leukemia (AML). Advances in next-generation sequencing (NGS) have revealed numerous recurrent mutations in genes such as FLT3, NPM1, DNMT3A, TP53, NRAS, and RUNX1. The acquisition order of gene mutations during MDS progression to leukemia is non-random and has prognostic significance. Understanding the molecular events behind MDS transformation to AML has paved the way for targeted and personalized treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jayastu Senapati, Koji Sasaki
Summary: Chronic myeloid leukemia is a genetically heterogeneous disease characterized by the presence of the Philadelphia chromosome and the BCR::ABL fusion protein. The disease is accompanied by chromosomal and genetic instability, leading to increased chromosomal abnormalities and other genetic aberrations. Understanding the cause and effects of this instability may improve treatment options for advanced phase CML.
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
Biochemistry & Molecular Biology
Phaedon D. D. Zavras, Ilias Sinanidis, Panagiotis Tsakiroglou, Theodoros Karantanos
Summary: Myelodysplastic syndrome (MDS) is a blood cancer characterized by bone marrow dysplasia and failure of hematopoiesis. Recent studies have shown that specific molecular abnormalities at earlier stages of MDS can predict progression to acute myeloid leukemia (AML). Different chromosomal abnormalities and somatic mutations present in MDS and AML-MRC have important prognostic implications. Changes in the classification of these neoplasms reflect the advances in understanding their biology. Novel therapeutic approaches, including adding venetoclax to hypomethylating agents and targeting specific mutations, have emerged for high-risk MDS and AML-MRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Oncology
Adelina Fernandes, Naranie Shanmuganathan, Susan Branford
Summary: This article discusses the genomic mechanisms of drug resistance in patients with chronic myeloid leukemia (CML), emphasizing the impact of genetic mutations on treatment response and drug resistance, as well as the potential role of expanded genomic testing in managing CML patients in the future.
Article
Hematology
Haley J. Abel, Karolyn A. Oetjen, Christopher A. Miller, Sai M. Ramakrishnan, Ryan B. Day, Nichole M. Helton, Catrina C. Fronick, Robert S. Fulton, Sharon E. Heath, Stefan P. Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J. Duncavage, Molly C. Schroeder, Jacqueline E. Payton, David H. Spencer, Matthew J. Walter, Peter Westervelt, John F. Dipersio, Timothy J. Ley, Daniel C. Link
Summary: TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants. The specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. NF1 and ETV6 mutations are highly enriched in TP53-mutated AML, and abnormal telomeric sequences were detected in the interstitial regions of chromosomes.
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
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)
Article
Oncology
Shyam A. Patel, Maxwell R. Lloyd, Jan Cerny, Qiming Shi, Karl Simin, Asiri Ediriwickrema, Lloyd Hutchinson, Patricia M. Miron, Anne W. Higgins, Muthalagu Ramanathan, Jonathan M. Gerber
Summary: TP53 disruptions are associated with mutations in epigenetic regulators, spliceosome machinery, and cohesin complex, but show low co-occurrence with mutations in proliferative signaling genes. High mutant TP53 gene dosage predicts low durability of remission. Treatment with hypomethylating agents can improve patient survival rates.
LEUKEMIA & LYMPHOMA
(2021)
Review
Oncology
Alexander J. Ambinder, Amy E. DeZern
Summary: Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms resulting from mutations in myeloid stem cells or progenitors. Although they differ in clinical and laboratory presentations, they are closely related through shared lineage and the presence of AML-like features in some MDS cases. Understanding the genetic distinctions and similarities between MDS and AML is crucial for refining prognostication, guiding disease management, and developing novel therapies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Ophthalmology
Alexandra Pietraszkiewicz, Freekje van Asten, Alan Kwong, Rinki Ratnapriya, Goncalo Abecasis, Anand Swaroop, Emily Y. Chew
Article
Biochemistry & Molecular Biology
S. Shabbeer, D. Omer, D. Berneman, O. Weitzman, A. Alpaugh, A. Pietraszkiewicz, S. Metsuyanim, A. Shainskaya, M. Z. Papa, R. I. Yarden
Article
Ophthalmology
Alexandra Pietraszkiewicz, Christopher Hampton, Sonny Caplash, Ling Lei, Yassemi Capetanaki, Gauri Tadvalkar, Sonali Pal-Ghosh, Mary Ann Stepp, Paola Bargagna-Mohan, Royce Mohan
EXPERIMENTAL EYE RESEARCH
(2019)
Article
Biophysics
Alexandra A. Pietraszkiewicz, Debbie Payne, Maria Abraham, Angel Garced, Krishna C. Devarasetty, Megan Wall, Supriya M. Menezes, Sveti Ugarte, Filip Pirsl, Sencer Goklemez, Frederick L. Ferris, John Barrett, Minoo Battiwalla, Richard W. Childs, Steven Z. Pavletic, Rachel J. Bishop
Summary: The study found a tendency towards ocular dryness in individuals with hematologic disorders preparing for HSCT based on differences in baseline ocular surface indicators; individuals who developed oGVHD showed changes in corneal staining score, Schirmer's test, and TBUT.
BONE MARROW TRANSPLANTATION
(2021)
Correction
Biophysics
Alexandra A. Pietraszkiewicz, Debbie Payne, Maria Abraham, Angel Garced, Krishna C. Devarasetty, Megan Wall, Supriya M. Menezes, Sveti Ugarte, Filip Pirsl, Sencer Goklemez, Frederick L. Ferris, John Barrett, Minoo Battiwalla, Richard W. Childs, Steven Z. Pavletic, Rachel J. Bishop
BONE MARROW TRANSPLANTATION
(2021)