Review
Oncology
Jeffery M. Klco, Charles C. Mullighan
Summary: This review emphasizes the different genetic pathways impacted by germline mutations leading to the development of familial and sporadic haematological malignancies, with a particular focus on recent advances in acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic syndromes.
NATURE REVIEWS CANCER
(2021)
Review
Oncology
Long Su, Yuan-Yuan Shi, Zeng-Yan Liu, Su-Jun Gao
Summary: This review summarizes the research progress and treatment methods of CEBPA gene mutations in AML, proposes a new treatment algorithm, and may be beneficial for further investigation and optimizing clinical management of AML patients with CEBPA mutations.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Peng Li, Sara Brown, Margaret Williams, Thomas White, Wei Xie, Wei Cui, Deniz Peker, Li Lei, Christian A. Kunder, Huan-You Wang, Sarah S. Murray, Jennie Vagher, Tibor Kovacsovics, Jay L. Patel
Summary: The study revealed significant differences between patients with HM carrying DDX41 CV and those with VUS, including older age, male predominance, frequent co-occurrence of somatic DDX41 variants, and lower somatic mutation burden in CV patients. These findings underscore the distinct clinical entity defined by germline DDX41 variants and emphasize the need for gene-specific diagnostic and clinical management guidelines.
Article
Genetics & Heredity
Abdulsamad Wafa, Belal Ali, Faten Moassass, Maged Kheder, Abdulmunim Aljapawe, Bassel Al-Halabi, Kristin Mrasek, Thomas Liehr, Walid Al-Achkar
Summary: This study investigated the CEBPA gene mutations in a Syrian family with AML. The results showed that all affected family members had a good response to chemotherapy and achieved complete remission. This research is important for understanding the relationship between CEBPA gene mutations and AML.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Medicine, Research & Experimental
Yizhen Li, Wentao Yang, Meenakshi Devidas, Stuart S. Winter, Chimene Kesserwan, Wenjian Yang, Kimberly P. Dunsmore, Colton Smith, Maoxiang Qian, Xujie Zhao, Ranran Zhang, Julie M. Gastier-Foster, Elizabeth A. Raetz, William L. Carroll, Chunliang Li, Paul P. Liu, Karen R. Rabin, Takaomi Sanda, Charles G. Mullighan, Kim E. Nichols, William E. Evans, Ching-Hon Pui, Stephen P. Hunger, David T. Teachey, Mary Relling, Mignon L. Loh, Jun J. Yang
Summary: Genetic alterations in the RUNX1 gene are associated with various blood disorders, especially those of the megakaryocyte and myeloid lineages. Germline RUNX1 variants have different effects on B-ALL and T-ALL, with the latter showing severe damaging effects. Additionally, JAK3 mutation is a common somatic genomic abnormality in T-ALL with germline RUNX1 variants.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Hematology
Sanne Noort, Jolieke van Oosterwijk, Jing Ma, Elizabeth A. R. Garfinkle, Stephanie Nance, Michael Walsh, Guangchun Song, Dirk Reinhardt, Martina Pigazzi, Franco Locatelli, Henrik Hasle, Jonas Abrahamsson, Marie Jarosova, Charikleia Kelaidi, Sophia Polychronopoulou, Marry M. van den Heuvel-Eibrink, Maarten Fornerod, Tanja A. Gruber, C. Michel Zwaan
Summary: Detecting genetic aberrations in pediatric acute myeloid leukemia through molecular profiling can provide valuable insights into the biology and clinical outcomes of the disease. This study successfully identified rearrangements and novel mutations in a cohort of pediatric AML patients. The detected aberrations showed distinct gene expression patterns and associations with other diseases such as Ewing sarcoma. The findings highlight the importance of using molecular profiling techniques for diagnostic purposes.
Article
Oncology
Owen J. Chen, Ester Castellsague, Mohamed Moustafa-Kamal, Javad Nadaf, Barbara Rivera, Somayyeh Fahiminiya, Yilin Wang, Isabelle Gamache, Caterina Pacifico, Lai Jiang, Jian Carrot-Zhang, Leora Witkowski, Albert M. Berghuis, Stefan Schoenberger, Dominik Schneider, Morten Hillmer, Susanne Bens, Reiner Siebert, Colin J. R. Stewart, Ziguo Zhang, William C. H. Chao, Celia M. T. Greenwood, David Barford, Marc Tischkowitz, Jacek Majewski, William D. Foulkes, Jose G. Teodoro
Summary: Two germline CDC20 missense variants that segregate with cancer in two families compromise the spindle assembly checkpoint and lead to aberrant mitotic progression, which could predispose cells to transformation.
Article
Biochemistry & Molecular Biology
Abhishek Niroula, Aswin Sekar, Mark A. Murakami, Mark Trinder, Mridul Agrawal, Waihay J. Wong, Alexander G. Bick, Md Mesbah Uddin, Christopher J. Gibson, Gabriel K. Griffin, Michael C. Honigberg, Seyedeh M. Zekavat, Kaavya Paruchuri, Pradeep Natarajan, Benjamin L. Ebert
Summary: Studies have shown that clonal hematopoiesis and mosaic chromosomal alterations are associated with lineage-specific hematologic malignancies, and these genetic alterations can be used in combination with blood count parameters to identify individuals at high risk.
Article
Hematology
Matilde Boada, Ana Ines Catalan, Carolina Ottati, Florencia Bentancour, Daniela Lens, Cecilia Guillermo, Sofia Grille
Summary: Myeloid neoplasms with germline predisposition were included in the 2016 World Health Organization classification of hematological malignancies, with CEBPA gene mutations being a driver for acute myeloid leukemia. Familial CEBPA AML shares characteristics with somatic CEBPA AML but has a higher relapse incidence.
HEMATOLOGY REPORTS
(2021)
Article
Cell Biology
Yi Chen, Yang Zhang, Zhihua Wang, Yewei Wang, Yujiao Luo, Nannan Sun, Shasha Zheng, Wenzhe Yan, Xiang Xiao, Sufang Liu, Ji Li, Hongling Peng, Yunxiao Xu, Guoyu Hu, Zhao Cheng, Guangsen Zhang
Summary: In this study, we investigated the clinical and hematological features of three genetically related families predisposed to myeloproliferative neoplasms (MPNs). We identified a mutation in the CHST15 gene, which resulted in increased JAK2V617F allele burden and upregulated p-Stat3 activity, leading to increased proliferative and prodifferentiation potential of transgenic cells.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Ji Yuan, Rong He, Hassan B. Alkhateeb
Summary: CEBPA gene mutation is a common genetic alteration in acute myeloid leukemia (AML), which can be associated with sporadic and familial AML. Recent advances in molecular testing and the prognostic role of CEBPA mutation have significantly changed the definition of AML-CEBPA. This review discusses the impact on laboratory evaluation and clinical management for sporadic and familial AML-CEBPA patients, as well as the assessment of minimal residual disease and stem cell transplant in selected AML-CEBPA patients.
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2023)
Article
Oncology
Amye M. Harrigan, Amy M. Trottier
Summary: Acute myeloid leukemia with germline CEBPA mutation is a subtype with a favorable prognosis, usually involving N-terminus germline variant and C-terminus somatic variant. However, there are rare cases with CEBPA germline variant in the C-terminus and somatic variant in the N-terminus. This case report highlights the differences in clinical outcomes and lifetime penetrance between N- and C-terminal germline variants, providing important information for patient management.
Article
Hematology
Hui Wei, Chunlin Zhou, Bingcheng Liu, Dong Lin, Yan Li, Shuning Wei, Benfa Gong, Guangji Zhang, Kaiqi Liu, Xiaoyuan Gong, Qiuyun Fang, Yuntao Liu, Shaowei Qiu, Runxia Gu, Zhen Song, Jiayuan Chen, Miao Yang, Junping Zhang, Jingjing Jin, Ying Wang, Yingchang Mi, Jianxiang Wang
Summary: This study found that the induction regimen and CSF3R mutations are independent prognostic factors for AML patients with CEBPAdm.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Svea Stratmann, Sara A. Yones, Markus Mayrhofer, Nina Norgren, Aron Skaftason, Jitong Sun, Karolina Smolinska, Jan Komorowski, Morten Krogh Herlin, Christer Sundstrom, Anna Eriksson, Martin Hoglund, Josefine Palle, Jonas Abrahamsson, Kirsi Jahnukainen, Monica Cheng Munthe-Kaas, Bernward Zeller, Katja Pokrovskaja Tamm, Lucia Cavelier, Linda Holmfeldt
Summary: AML is the leading cause of death in adult and pediatric patients, with specific differences in mutational spectrum at relapse. Key genes ARID1A and CSF1R show recurrent mutations at relapse, while new gene mutations identified may play important roles in disease progression and therapy resistance, providing possibilities for personalized medicine.
Article
Oncology
Xiong-yu Liao, Jian-pei Fang, Dun-hua Zhou, Kun-yin Qiu
Summary: CEBPA mutations are associated with a better prognosis in pediatric AML patients, even in the presence of FLT3/ITD mutations. Stem cell transplantation may not be necessary for pediatric AML patients with coexistence of CEBPA and FLT3/ITD mutations.
HEMATOLOGICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
J. Bar, W. Kian, M. Wolner, S. Derijcke, N. Girard, Y. Rottenberg, E. Dudnik, G. Metro, M. J. Hochmair, F. Aboubakar, K. Cuppens, L. Decoster, M. Reck, D. Limon, A. Calles Blanco, C. Astaras, S. Hafliger, N. Peled, A. Addeo
ANNALS OF ONCOLOGY
(2021)
Meeting Abstract
Oncology
Sajeve Samuel Thomas, Gino Kim In, Bernard Doger, Simon Haefliger, Juan Martin-Liberal, Zelanna Goldberg, Alex Cacovean, Rana Fiaz, Guang Chen, Madan H. Jagasia, Friedrich Graf Finckenstein, Maria Fardis, Antonio Jimeno
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Meeting Abstract
Oncology
Alfredo Addeo, Markus Joerger, Sacha Rothschild, Eric I. Eboulet, Gilles Godar, Christine Waibel-Pachinger, Simon Haefliger, Michael Thomas Mark, Eugenio Fernandez, Nicolas Mach, Laetitia A. Mauti, Martin Frueh
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Meeting Abstract
Oncology
Adam Schoenfeld, Sylvia Lee, Luis Paz-Ares, Bernard Doger, Scott Gettinger, Simon Haefliger, Angela Orcurto, Ammar Sukari, Sophie Papa, Juan Francisco Rodriguez Moreno, Friedrich Graf Finckenstein, Madan Jagasia, Rana Fiaz, Giri Sulur, Guang Chen, Viktoria Gontcharova, Kai He
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Fanny S. Krebs, Christian Britschgi, Sylvain Pradervand, Rita Achermann, Petros Tsantoulis, Simon Haefliger, Andreas Wicki, Olivier Michielin, Vincent Zoete
Summary: Alterations in the BRAF kinase can activate the MAP kinase signaling pathway and render cells sensitive to targeted therapy. Identifying the class of a BRAF mutation allows for personalized treatment strategies to be proposed. Developing predictive tools based on machine learning approaches can aid oncologists in tackling potential pathogenic BRAF mutations.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Murielle N. Wahli, Stefanie Hayoz, Dennis Hoch, Christoph O. Ryser, Michele Hoffmann, Amina Scherz, Birgit Schwacha-Eipper, Simon Haefliger, Julian Wampfler, Martin D. Berger, Urban Novak, Berna C. Oezdemir
Summary: The role of immune checkpoint inhibitors (ICI) in clinical practice was investigated in this study, focusing on patient and tumor characteristics, survival rates, and toxicity rates by sex. The results showed that ICI treatment had an increasing importance in oncology, with higher incidence of adverse events in female patients and associated with longer overall survival.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Jair Bar, Nir Peled, Shiruyeh Schokrpur, Mirjana Wolner, Ofer Rotem, Nicolas Girard, Frank Aboubakar Nana, Sofie Derijcke, Waleed Kian, Sandip Patel, Hadas Gantz-Sorotsky, Alona Zer, Mor Moskovitz, Giulio Metro, Yakir Rottenberg, Antonio Calles, Maximilian Hochmair, Kristof Cuppens, Lynn Decoster, Martin Reck, Dror Limon, Estelamari Rodriguez, Christoforos Astaras, Adrienne Bettini, Simon Hafliger, Alfredo Addeo
Summary: This study aimed to collect real-world data on osimertinib treatment for patients with uncommon EGFR mutations (ucEGFRmuts). The results showed that osimertinib has a high rate of disease control, both systemically and intracranially, in patients with ucEGFRmuts. The study also identified several resistance mechanisms.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Alfredo Addeo, Sacha Rothschild, Lisa Holer, Martina Schneider, Christine Waibel, Simon Haefliger, Michael Mark, Eugenio Fernandez, Nicolas Mach, Laetitia Mauti, Philip M. Jermann, Ilaria Alborelli, Byron Calgua, Spasenija Savic-Prince, Markus Joerger, Martin Frueh
Summary: The study showed that rogaratinib had minimal impact on improving PFS in patients with advanced SQCLC overexpressing FGFR mRNA, with common treatment-related adverse events.
Article
Biochemistry & Molecular Biology
Adrienne Vancura, Alejandro H. Gutierrez, Thorben Hennig, Carlos Pulido-Quetglas, Frank J. Slack, Rory Johnson, Simon Haefliger
Summary: This study has found a bias in the evaluation of evolutionary conservation for cancer-related lncRNAs, raising doubts about its relevance in cancer research.
Article
Oncology
Markus Joerger, Thomas Hundsberger, Simon Haefliger, Roger von Moos, Andreas F. Hottinger, Thomas Kaindl, Marc Engelhardt, Michalina Marszewska, Heidi Lane, Patrick Roth, Anastasios Stathis
Summary: The purpose of this study was to evaluate the safety, tolerability and antitumor activity of lisavanbulin as a 48-hour intravenous infusion at the recommended Phase 2 dose. The study included patients with ovarian, fallopian-tube, or primary peritoneal cancer as well as glioblastoma patients. The results showed that lisavanbulin was well tolerated and exhibited some antitumor activity in patients.
INVESTIGATIONAL NEW DRUGS
(2023)
Meeting Abstract
Oncology
Dagmar Hess, Ilaria Colombo, Simon Haefliger, Manuela Rabaglio, Sara Bastian, Michael Schwitter, Katrin Eckhardt, Jesus Glaus Garzon, Stefanie Hayoz, Christoph Kopp, Lisa Holer, Anna Mc Laughlin, Charlotte Kloft, Cristiana Sessa, Anastasios Stathis, Stefan Halbherr, Christian Baumgartner, Markus Joerger
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
S. Gettinger, H. Kluger, A. Schoenfeld, A. Betof Warner, K. He, A. Sukari, S. Thomas, B. Doger, S. Lee, S. Haefliger, Z. Goldberg, A. Cacovean, R. Fiaz, G. Chen, M. Jagasia, F. Graf Finckenstein, M. Fardis, A. Jimeno
JOURNAL OF THORACIC ONCOLOGY
(2021)
Meeting Abstract
Oncology
Scott Gettinger, Harriet Kluger, Adam Schoenfeld, Allison Betof-Warner, Kai He, Ammar Sukari, Bernard Doger de Speville Uribe, Sylvia Lee, Simon Haefliger, Zelanna Goldberg, Alex Cacovean, Rana Fiaz, Guang Chen, Madan Jagasia, Friedrich Graf Finckenstein, Maria Fardis, Antonio Jimeno
Meeting Abstract
Oncology
S. Gettinger, H. Kluger, A. Schoenfeld, A. Betof Warner, K. He, A. Sukari, S. S. Thomas, B. Doger de Speville, S. Lee, S. Haefliger, Z. Goldberg, A. Cacovean, R. Fiaz, G. Chen, M. Jagasia, F. Graf Finckenstein, M. Fardis, A. Jimeno
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adrienne Vancura, Andres Lanzos, Nuria Bosch-Guiteras, Monica Torres Esteban, Alejandro H. Gutierrez, Simon Haefliger, Rory Johnson
Summary: Long non-coding RNAs (lncRNAs) are key players in cancer and Cancer LncRNA Census 2 (CLC2) is a large and high-quality collection of cancer lncRNAs, demonstrating their evolutionary and clinical significance for precision medicine.