Article
Immunology
Dongbei Li, Haijun Li, Cheng Cheng, Gangping Li, Fangfang Yuan, Ruihua Mi, Xiaojiao Wang, Ding Li, Ruihua Fan, Xudong Wei
Summary: The combination therapy of all-trans retinoic acid (ATRA) and ABT-199 shows a synergistic antileukemic effect by inducing apoptosis and cell cycle arrest in acute myeloid leukemia (AML) cells. In vivo, this combination therapy prolongs the survival of AML xenograft mice. The study provides a potential treatment strategy and theoretical support for overcoming the clinical ABT-199 resistance problem in AML patients.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. Wong, Charlie Hatton, Christian Marinaccio, Florian Perner, Masooma Rajput, Noa J. C. Antonissen, Yanhe Wen, Lu Yang, Lorenzo Brunetti, Chun -Wei Chen, Scott A. Armstrong
Summary: The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Most patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1, with an NPM1 mutation (NPM1c) being common in these cases. This study reveals that NPM1c directly binds to specific chromatin targets, collaborates with the MLL1 complex, and directly regulates oncogenic gene expression in AML.
Article
Medicine, General & Internal
Pau Montesinos, Christian Recher, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Giambattista Bertani, Michael Heuser, Rodrigo T. Calado, Andre C. Schuh, Su-Peng Yeh, Scott R. Daigle, Jianan Hui, Shuchi S. Pandya, Diego A. Gianolio, Stephane de Botton, Hartmut Dohner
Summary: This study demonstrated that the combination therapy of oral ivosidenib and azacitidine showed better event-free survival and longer overall survival in patients with newly diagnosed IDH1-mutated acute myeloid leukemia.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Xue Qing David Wang, Dandan Fan, Qinyu Han, Yiman Liu, Hongzhi Miao, Xinyu Wang, Qinglan Li, Dong Chen, Haley Gore, Pamela Himadewi, Gerd P. Pfeifer, Tomasz Cierpicki, Jolanta Grembecka, Jianzhong Su, Shasha Chong, Liling Wan, Xiaotian Zhang
Summary: Nucleophosmin (NPM1) is a nucleolar protein with various functions, and its mutation is commonly found in acute myeloid leukemia (AML). This study shows that mutant NPM1 directly binds to active chromatin regions and controls the transcription of AML-driving genes. These findings provide insights into the mechanism behind AML caused by NPM1 mutation and suggest potential therapeutic interventions.
Article
Pediatrics
Jong Hyeon Lee, Jong Ho Lee, Jae Min Lee
Summary: While ATRA is effective in treating APL, it may lead to side effects such as hearing loss. This case demonstrates that reducing the dose of ATRA and administering dexamethasone can successfully reverse ATRA-associated hearing loss. Conducting a randomized clinical trial using dexamethasone in combination with ATRA is recommended to prevent hearing loss caused by ATRA.
Article
Pharmacology & Pharmacy
Xiao Liu, Lili Zhang, Yueying Yang, Weiwei Yin, Yunhu Liu, Chunyi Luo, Ruizhe Zhang, Zhiguo Long, Yanyan Jiang, Bing Wang
Summary: Arsenic trioxide (ATO) has been clinically used as a reliable and effective frontline drug for the treatment of acute promyelocytic leukemia (APL). However, its administration regimen is limited due to fast clearance, short therapeutic window, and toxicity. This study developed transferrin-modified liposomes encapsulating AsIII to improve its therapeutic efficacy. The AsIII-loaded liposomes exhibited acid-sensitive release and specifically targeted APL cells, leading to apoptosis and cell differentiation. Combining transferrin-modified retinoic acid liposomes further enhanced the tumor inhibition effect. The results suggest that transferrin-modified AsIII liposomes could be a novel clinical strategy for APL treatment with reduced systemic toxicity and improved efficacy.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Oncology
Maria Hernandez-Valladares, Rebecca Wangen, Elise Aasebo, Hakon Reikvam, Frode S. Berven, Frode Selheim, Oystein Bruserud
Summary: ATRA/VP combination therapy has shown effectiveness in stabilizing AML in some patients, including those with chemoresistant relapse. Furthermore, combining new and less intensive antileukemic therapies with ATRA/VP may represent a new therapeutic strategy in AML. Proteomic/phosphoproteomic profiling can be used for the early identification of responders to ATRA/VP-based treatment.
Article
Multidisciplinary Sciences
Yijia Tang, Xin Tian, Zihan Xu, Junke Cai, Han Liu, Nan Liu, Zhu Chen, Saijuan Chen, Feng Liu
Summary: ATRA can induce near-normal differentiation towards mature granulocytes in APL/AML-M3 cells, but induces incomplete and promiscuous differentiation in AML-M2 cells, characterized by coinduction of myelopoiesis and lymphopoiesis gene expression programs.
Review
Chemistry, Medicinal
Oystein Bruserud, Galina Tsykunova, Maria Hernandez-Valladares, Hakon Reikvam, Tor Henrik Anderson Tvedt
Summary: Despite undergoing allogeneic stem cell transplantation, AML patients still face issues such as chemo-resistant leukemia relapse and transplant-related mortality.
Article
Hematology
Hong-Hu Zhu, Ya-Z hen Qin, Zhang-Lin Zhang, Yong-Jing Liu, Li-Jun Wen, M. James You, Cheng Zhang, Esperanza Such, Hong Luo, Hong-Jian Yuan, Hong-Sheng Zhou, Hong-Xing Liu, Reng Xu, Ji Li, Jian-Hu Li, Jian-Ping Hao, Jie Jin, Liang Yu, Jing-Ying Zhang, Li-Ping Liu, Le-Ping Zhang, Rui-Bin Huang, Shu-Hong Shen, Su-Jun Gao, Wei Wang, Xiao-Jing Yan, Xin-You Zhang, Xin Du, Xiao-Xia Chu, Yan-Fang Yu, Yi Wang, Ying-Chang Mi, Ying Lu, Zhen Cai, Zhan Su, David Christopher Taussig, Suzanne MacMahon, Edward D. Ball, Huan-You Wang, John S. Welch, C. Cameron Yin, Gautam Borthakur, Miguel A. Sanz, Hagop M. Kantarjian, Jin-Yan Huang, Jiong Hu, Su-Ning Chen
Summary: AML with RARG rearrangement is a subtype similar to classic acute promyelocytic leukemia but shows insensitivity to ATRA and ATO treatment. This study aims to define the clinicopathological features, genomic landscape, and outcomes of AML with RARG rearrangements. The study identified 34 patients with AML with RARG rearrangements, and their prognosis was found to be poor, with a high mortality rate and low survival rates.
Review
Oncology
Dong-Yeop Shin
Summary: The TP53 gene is frequently mutated in various human cancers and is the first tumor suppressor gene discovered. Mutations within the DNA-binding domain of TP53 result in loss of DNA-binding capability of p53 protein. However, the phenotypic landscape of TP53 mutations is complex and presents a significant challenge in developing effective treatment strategies. TP53-mutated AML is associated with poor prognosis and is classified as a distinct subgroup within AML. Current standard treatments are largely ineffective for TP53-mutated AML, and there is an urgent need for novel treatment approaches.
Article
Chemistry, Medicinal
Laia Josa-Cullere, Katrina S. Madden, Thomas J. Cogswell, Thomas R. Jackson, Tom S. Carter, Douzi Zhang, Graham Trevitt, Stephen G. Davies, Paresh Vyas, Graham M. Wynne, Thomas A. Milne, Angela J. Russell
Summary: A novel compound, OXS007417, identified through a phenotypic high-throughput screen, shows promise in decreasing tumor volume in acute myeloid leukemia.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Pei-Yuan Yin, Rui-Wen Wang, Rui Jing, Xing Li, Jing-Hua Ma, Kai-Min Li, Hua Wang
Summary: Acute myeloid leukemia (AML) is extensively studied at the cellular and molecular levels, with cytogenetic markers being important for diagnosis, prognosis stratification and treatment. However, new technologies have revealed the significance of other molecular markers, such as gene mutations and epigenetic changes, in understanding the disease. Identifying new AML biomarkers contributes to better understanding and individualized treatment.
FRONTIERS IN ONCOLOGY
(2023)
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)
Article
Immunology
Xueyan Li, Xiaoqi Luo, Siru Chen, Jiayi Chen, Xue Deng, Jiahui Zhong, Hui Wu, Xuhui Huang, Changjun Wang
Summary: Hepatocellular carcinoma is characterized by high infiltration of myeloid-derived suppressor cells (MDSCs), which are key drivers of maintaining the immunosuppressive tumor microenvironment. All-trans retinoic acid (ATRA) can differentiate MDSCs into mature myeloid cells, but its effect on liver cancer growth inhibition is unknown.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Editorial Material
Hematology
Attilio Orazi, Robert P. Hasserjian, Mario Cazzola, Hartmut Dohner, Ayalew Tefferi, Daniel A. Arber
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Volker Arndt, Daniela Doege, Stefan Froehling, Peter Albers, Hana Alguel, Ralf Bargou, Carsten Bokemeyer, Martin Bornhaeuser, Christian H. Brandts, Peter Brossart, Sara Yvonne Brucker, Tim H. Bruemmendorf, Hartmut Doehner, Norbert Gattermann, Michael Hallek, Volker Heinemann, Ulrich Keilholz, Thomas Kindler, Cornelia von Levetzow, Florian Lordick, Ulf Peter Neumann, Christoph Peters, Dirk Schadendorf, Stephan Stilgenbauer, Thomas Zander, Daniel Zips, Delia Braun, Thomas Seufferlein, Gerd Nettekoven, Michael Baumann
Summary: The capacities of German Comprehensive Cancer Centers (CCCs) in various aspects of oncology care were significantly affected during the first 2 years of the COVID-19 pandemic. Follow-up, psycho-oncologic care, and tumor surgery were particularly impacted, along with other areas of multidisciplinary oncological care. This study highlights the importance of developing strategies to prevent similar limitations in the future.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Letter
Hematology
Andrew H. Wei, Hartmut Doehner, Hamid Sayar, Farhad Ravandi, Pau Montesinos, Herve Dombret, Dominik Selleslag, Kimmo Porkka, Jun-Ho Jang, Barry Skikne, C. L. Beach, Thomas Prebet, George Zhang, Alberto Risueno, Manuel Ugidos, Wendy L. See, Daniel Menezes, Gail J. Roboz
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Christopher M. Arends, Thomas G. Liman, Paulina M. Strzelecka, Anna Kufner, Pelle Loewe, Shufan Huo, Catarina M. Stein, Sophie K. Piper, Marlon Tilgner, Pia S. Sperber, Savvina Dimitriou, Peter U. Heuschmann, Raphael Hablesreiter, Christoph Harms, Lars Bullinger, Joachim E. Weber, Matthias Endres, Frederik Damm
Summary: Clonal hematopoiesis (CH) is common among older people and is associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. This study investigated CH in patients with first-ever ischemic stroke and found that CH is associated with an increased risk of recurrent vascular events and death.
Article
Oncology
J. Weller, N. Schaefer, C. Schaub, T. Tzaridis, T. Zeyen, M. Schneider, A. L. Potthoff, F. A. Giordano, J. P. Steinbach, P. S. Zeiner, T. Kowalski, M. Sabel, P. Hau, D. Krex, O. Grauer, R. Goldbrunner, O. Schnell, G. Tabatabai, F. Ringel, F. Schmidt-Graf, S. Brehmer, J. C. Tonn, L. Bullinger, P. Vajkoczy, M. Glas, H. Vatter, U. Herrlinger, C. Seidel
Summary: In the CeTeG/NOA-09 randomized phase III trial, TMZ/CCNU combination therapy was found to be superior to TMZ in newly diagnosed MGMT methylated glioblastoma, with higher incidence of hematotoxicity. This study analyzed high-grade hematotoxicity and its prognostic relevance in the trial population.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Oncology
Victoria Y. Ling, Jasmin Straube, William Godfrey, Rohit Haldar, Yashaswini Janardhanan, Leanne Cooper, Claudia Bruedigam, Emily Cooper, Paniz Tavakoli Shirazi, Sebastien Jacquelin, Siok-Keen Tey, Jonathan Baell, Fei Huang, Jianwen Jin, Yichao Zhao, Lars Bullinger, Megan J. Bywater, Steven W. Lane
Summary: This study identifies defective cell cycle arrest as a clinically relevant contributor to chemoresistance in acute myeloid leukemia (AML). Downregulation of CDKN2A is associated with inferior overall survival in AML patients and occurs at relapse. Therapeutic targeting of the G(1)S cell cycle restriction point and promotion of apoptosis can enhance chemotherapy response in AML.
Article
Oncology
Jasmin Straube, Theresa Eifert, Therese Vu, Yashaswini Janardhanan, Rohit Haldar, Bjoern von Eyss, Leanne Cooper, Claudia Bruedigam, Victoria Y. Ling, Emily Cooper, Ann-Marie Patch, Lars Bullinger, Tina M. Schnoeder, Megan Bywater, Florian H. Heidel, Steven W. Lane
Summary: Murine models are useful for studying AML subtypes and compound mutations. The Cre recombinase expression in a transgenic murine model can lead to aggressive leukemia phenotype, polyclonal expansion of FLT3(ITD/ITD) progenitor cells, differentiation block and activation of Myc-dependent gene expression programs. Our report highlights the potential risks and unexpected effects of Cre expression in investigating oncogenic mutations in murine cancer models.
Article
Hematology
Elisa Donato, Nadia Correia, Carolin Andresen, Darja Karpova, Roberto Wuerth, Corinna Klein, Markus Sohn, Adriana Przybylla, Petra Zeisberger, Kathrin Rothfelder, Helmut Salih, Halvard Bonig, Sebastian Stasik, Christoph Roellig, Anna Dolnik, Lars Bullinger, Frank Buchholz, Christian Thiede, Daniel Huebschmann, Andreas Trumpp
Summary: This study proposes a novel flow cytometry sorting strategy for CD34 neg AML subtypes, enriching for leukemic stem cells (LSCs) independently of CD34 status by positive selection for GPR56 and negative selection for NKG2D ligands. The functional reconstitution capacity and transcriptomes of CD34- and CD34+ LSCs are shown to be similar, supporting the concept of phenotypic plasticity. Patients with AML who still retain functional hematopoietic stem cells (HSCs) at the time of diagnosis have longer relapse-free and overall survival.
Article
Cardiac & Cardiovascular Systems
Alessia Lena, Ursula Wilkenshoff, Sara Hadzibegovic, Jan Porthun, Lukas Roesnick, Ann-Kathrin Froehlich, Tanja Zeller, Mahir Karakas, Ulrich Keller, Johann Ahn, Lars Bullinger, Hanno Riess, Stuart D. Rosen, Alexander R. Lyon, Thomas F. Luescher, Matthias Totzeck, Tienush Rassaf, Daniel Burkhoff, Mandeep R. Mehra, Jeroen J. Bax, Javed Butler, Frank Edelmann, Wilhelm Haverkamp, Stefan D. Anker, Milton Packer, Andrew J. S. Coats, Stephan von Haehling, Ulf Landmesser, Markus S. Anker
Summary: This study found that cancer patients have cardiac wasting and decreased heart function. Low left ventricular mass is associated with poor functional status and increased all-cause mortality in cancer patients.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Geriatrics & Gerontology
Markus S. Anker, Alessia Lena, Eric J. Roeland, Jan Porthun, Sebastian Schmitz, Sara Hadzibegovic, Philipp Sikorski, Ursula Wilkenshoff, Ann-Kathrin Froehlich, Luisa Valentina Ramer, Matthias Rose, Jan Eucker, Tienush Rassaf, Matthias Totzeck, Lorenz H. Lehmann, Stephan von Haehling, Andrew J. S. Coats, Tim Friede, Javed Butler, Stefan D. Anker, Hanno Riess, Ulf Landmesser, Lars Bullinger, Ulrich Keller, Johann Ahn
Summary: The patient-reported ability to walk 4 m and wash oneself is an independent predictor of survival and associated with decreased functional status in pre-terminal cancer patients.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Geriatrics & Gerontology
Sara Hadzibegovic, Jan Porthun, Alessia Lena, Pia Weinlaender, Laura C. Lueck, Sophia K. Potthoff, Lukas Roesnick, Ann-Kathrin Froehlich, Luisa Valentina Ramer, Frederike Sonntag, Ursula Wilkenshoff, Johann Ahn, Ulrich Keller, Lars Bullinger, Amir A. Mahabadi, Matthias Totzeck, Tienush Rassaf, Stephan von Haehling, Andrew J. S. Coats, Stefan D. Anker, Eric J. Roeland, Ulf Landmesser, Markus S. Anker
Summary: This study aimed to evaluate the prognostic value of hand grip strength (HGS) in cancer patients and establish reference values for a European-based population. The study found that reduced HGS was associated with increased mortality, decreased overall functional status, and decreased physical performance in cancer patients, regardless of cachexia.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Oncology
Theresa Eifert, Chen-Jen Hsu, Alicia L. Becker, Sarah Graessle, Arik Horne, Franziska Bemmann, Qirui Zhang, Michael Heuser, Valeri Vasioukhin, Sebastian Scholl, Andreas Hochhaus, Florian Siegerist, Nicole Endlich, Lars Bullinger, Steven W. Lane, Simon Haas, Tina M. Schnoeder, Florian H. Heidel
Summary: The Scribble complex proteins play a crucial role in hematopoietic cell fate decisions and self-renewal capacity. Through genetic screening, LLGL1 has been identified as a specific dependency and putative target in AML, with its inactivation leading to loss of stemness-associated gene-expression and induction of a specific phenotype in leukemia stem cells. These findings highlight the importance of LLGL1 and its cell-type specific functions in AML.
Article
Public, Environmental & Occupational Health
Asa Grauman, Mika Kontro, Karl Haller, Samantha Nier, Sofia Aakko, Katharina Lang, Chiara Zingaretti, Elena Meggiolaro, Silvia De Padova, Giovanni Marconi, Giovanni Martinelli, Caroline A. Heckman, Giorgia Simonetti, Lars Bullinger, Ulrik Kihlbom
Summary: This study aimed to explore patients' perceptions about precision medicine and their preferences for involvement in decision-making. Interviews were conducted with patients in Finland, Italy, and Germany, and thematic content analysis was used for data analysis. The results showed that patients' lack of knowledge hindered their involvement in decision-making. Treatment decisions were often based on intuition and trust rather than information, especially in situations where the patient's decision capacity was compromised. The study highlighted the importance of the physician's role as an expert and trusted individual in medical decision-making.
PATIENT EDUCATION AND COUNSELING
(2023)
Article
Oncology
Maximilian Schmutz, Manuela Zucknick, Richard F. Schlenk, Daniel Mertens, Axel Benner, Dieter Weichenhan, Oliver Muecke, Konstanze Doehner, Christoph Plass, Lars Bullinger, Rainer Claus
Summary: In this study, the researchers investigated whether unbiased genome-wide assessment of pre-treatment DNA methylation profiles can help identify AML patients who will achieve remission after an azacytidine-containing induction regimen. They found that some AML patients benefit from this treatment, but no predictive biomarkers for therapy response exist. The researchers also evaluated the value of a whole genome methyl-CpG screening assay and compared the discriminatory power of differentially methylated regions (DMRs) and single CpGs for predicting therapy response. The results suggest that a predictive epigenotype carries its methylation information at a complex, genome-wide level. However, the specificity of the predictive response to therapy was lacking for treatment with azacytidine.
CLINICAL EPIGENETICS
(2023)
Article
Hematology
Victoria Panagiota, Johanna Franziska Kerschbaum, Olaf Penack, Catarina M. Stein, Christopher M. Arends, Christian Koenecke, Paulina M. Strzelecka, Arnold Kloos, Laura Wiegand, Alina Lasch, Robert Altwasser, Adriane Halik, Razif Gabdoulline, Julia Thomson, Konstantin Weibl, Georg-Nikolaus Franke, Carolina Berger, Justin Hasenkamp, Francis Ayuk, Il-Kang Na, Gernot Beutel, Ulrich Keller, Lars Bullinger, Gerald Georg Wulf, Nicolaus Kroeger, Vladan Vucinic, Michael Heuser, Frederik Damm
Summary: Recent evidence suggests that clonal hematopoiesis (CH) does not significantly affect the safety, efficacy, or outcome of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia.