Article
Multidisciplinary Sciences
Osvaldo D. Rivera, Michael J. Mallory, Mathieu Quesnel-ValliIres, Rakesh Chatrikhi, David C. Schultz, Martin Carroll, Yoseph Barash, Sara Cherry, Kristen W. Lynch
Summary: In acute myeloid leukemia, alternative splicing events can alter the expression of a subset of genes independently of known somatic mutations. Furthermore, the reduced functional EZH2 in some patients is not solely caused by somatic mutations, indicating a role of aberrant splicing in gene dysregulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Zivojin Jevtic, Vittoria Matafora, Francesca Casagrande, Fabio Santoro, Saverio Minucci, Massimilliano Garre, Milad Rasouli, Olaf Heidenreich, Giovanna Musco, Juerg Schwaller, Angela Bachi
Summary: The study reveals that the NUP98-NSD1 fusion protein plays a transformative role in hematopoietic cells through its interaction and colocalization with SMARCA5. The formation of NUP98-NSD1 nuclear condensates is not enough to maintain the transformed phenotype, suggesting that selectively targeting condensate constituents could be a new therapeutic strategy for NUP98-NSD1 driven AML.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
A. A. Bessonova, L. G. Ghukasyan, L. Baidun, A. Chudinov, T. Nasedkina
Summary: A method has been developed for identifying the chimeric transcript NUP98-NSD1 in children with acute myeloid leukemia, utilizing a combination of reverse transcription-polymerase chain reaction and allele-specific hybridization on a biological microchip.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
(2021)
Article
Hematology
Chi-Keung Cheng, Hoi-Yun Chan, Yuk-Lin Yung, Thomas S. K. Wan, Alex W. K. Leung, Chi-Kong Li, Ke Tian, Natalie P. H. Chan, Joyce S. Cheung, Margaret H. L. Ng
Summary: In this study, a NUP98-JADE2 fusion was identified in a pediatric AML patient showing APL-like features. The fusion was found to impair ATRA-mediated transcriptional control and myeloid differentiation. Additionally, the fusion altered the subcellular distribution of JADE2, leading to attenuated ATRA-induced responses and myeloid activation. This is the first report of a NUP98-non-RAR rearrangement in a case resembling APL, indicating the involvement of JADE2 in retinoic acid-induced differentiation.
Article
Hematology
Danyang Wu, Ran Gao
Summary: This study presents a case of acute myeloid leukemia with the t(11;12)(p15;q13) translocation, exhibiting characteristics consistent with acute promyelocytic leukemia (APL). RNA sequencing analysis revealed the presence of the NUP98-retinoic acid receptor gamma (RARG) gene resulting from the translocation. Moreover, a mutation in the ARID1B gene suggests a potential association with resistance to all-trans retinoic acid (ATRA).
Article
Oncology
Wei Xie, Philipp W. Raess, Jennifer Dunlap, Cristina Magallanes Hoyos, Hongmei Li, Peng Li, Ronan Swords, Susan B. Olson, Fei Yang, Tauangtham Anekpuritanang, Shimin Hu, Joanna Wiszniewska, Guang Fan, Richard D. Press, Stephen R. Moore
Summary: Adult AML-NUP98 is associated with an unfavorable outcome, often accompanied by cryptic translocations. Our study suggests that incorporating the NUP98 probe into AML FISH panels are warranted to improve clinical management.
LEUKEMIA & LYMPHOMA
(2022)
Article
Biochemistry & Molecular Biology
Carmelo Gurnari, Simona Pagliuca, Valeria Visconte
Summary: Alternative RNA splicing is an essential physiological function that plays a crucial role in cellular development. RNA splicing dysfunction has been implicated in the development of several cancers, including myeloid malignancies. Cancer cells exhibit marked gene expression alterations, including different usage of AS isoforms, potentially causing tissue-specific effects and disruptions of downstream pathways.
Article
Oncology
Marco Tembrink, Wanda Maria Gerding, Stefan Wieczorek, Thomas Mika, Roland Schroers, Huu Phuc Nguyen, Deepak Ben Vangala, Verena Nilius-Eliliwi
Summary: Optical genome mapping (OGM) has shown potential for improving genetic diagnostics in acute myeloid leukemia (AML). In this study, OGM was used to detect genome-wide structural variants and monitor disease progression. A previously unknown NUP98::ASH1L fusion was identified in an adult patient with secondary AML, resulting from a complex rearrangement between chromosomes 1 and 11. OGM proved to be a valuable tool for cytogenetic diagnostics in AML, especially for detecting rare structural variants and tracking clonal evolution during the course of the disease.
Article
Medicine, Research & Experimental
Fang-Min Zhong, Fang-Yi Yao, Jing Liu, Mei-Yong Li, Jun-Yao Jiang, Ying Cheng, Shuai Xu, Shu-Qi Li, Nan Zhang, Bo Huang, Xiao-Zhong Wang
Summary: This study investigates the relationship between splicing factors (SFs) and the clinical features and biological processes of AML. The majority of SFs were upregulated in AML samples and associated with poor prognosis. A risk score model was constructed as an independent prognostic factor, and SRSF10 was identified as a potential therapeutic target and biomarker for AML.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Genetics & Heredity
Giuseppina Conteduca, Barbara Testa, Chiara Baldo, Alessia Arado, Michela Malacarne, Giovanni Candiano, Andrea Garbarino, Domenico A. Coviello, Claudia Cantoni
Summary: The NSD1 gene encodes a methyltransferase involved in embryonic development. Pathogenic variants of NSD1 gene lead to Sotos syndrome and have been found in certain types of cancer. This study investigates NSD1 mRNA expression in cells from Sotos patients and healthy controls, identifying new mRNA isoforms and mutations associated with decreased NSD1 levels.
Review
Oncology
Yotaro Ochi, Seishi Ogawa
Summary: Recent genomic studies have identified chromatin-spliceosome (CS)-acute myeloid leukemia (AML) as a new subgroup of AML defined by mutations affecting epigenetic regulation. CS-AML shares molecular similarities with myelodysplastic syndrome and secondary AML and is associated with poor prognosis, requiring novel therapeutic strategies and stem cell transplantation. Multiple CS-mutations synergistically contribute to the development of severe MDS/AML, highlighting the importance of these mutations in disease progression.
Article
Biochemistry & Molecular Biology
Chuan Wu, Jieke Cui, Yankun Huo, Luyao Shi, Chong Wang
Summary: This research aimed to understand the mechanism underlying the self-renewal capacity of leukemic stem cells (LSCs) in order to provide new insights into the treatment of acute myeloid leukemia (AML). The study found that HOXB-AS3 and YTHDC1 were robustly induced in AML and correlated with adverse prognosis. YTHDC1 was found to bind HOXB-AS3 and regulate its expression, promoting the proliferation of LSCs and impairing apoptosis, thus accelerating AML progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Oncology
Juan Zhang, Xuefeng Gao, Li Yu
Summary: Accurate orchestration of gene expression is critical for normal hematopoiesis, with epigenetic aberration being a major cause of AML. HDACs play pivotal roles in chromatin remodeling, regulating stemness maintenance, cell fate determination, proliferation, and differentiation, with potential implications in carcinogenesis. Targeting the interactions between HDACs and oncogenic proteins could provide insights for AML treatment strategies.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Article
Hematology
Eline J. M. Bertrums, Jenny L. Smith, Lauren Harmon, Rhonda E. Ries, Yi-Cheng J. Wang, Todd A. Alonzo, Andrew J. Menssen, Karen M. Chisholm, Amanda R. Leonti, Katherine Tarlock, Fabiana Ostronoff, Era L. Pogosova-Agadjanyan, Gertjan J. L. Kaspers, Henrik Hasle, Michael Dworzak, Christiane Walter, Nora Muehlegger, Cristina Morerio, Laura Pardo, Betsy Hirsch, Susana Raimondi, Todd M. Cooper, Richard Aplenc, Alan S. Gamis, Edward A. Kolb, Jason E. Farrar, Derek Stirewalt, Xiaotu Ma, Tim I. Shaw, Scott N. Furlan, Lisa Eidenschink Brodersen, Michael R. Loken, Marry M. van den Heuvel-Eibrink, C. Michel Zwaan, Timothy J. Triche, Bianca F. Goemans, Soheil Meshinchi
Summary: NUP98 fusions are rare recurrent alterations in AML, associated with adverse outcomes. Through comprehensive analysis, we found that patients with different fusion partners have distinct characteristics and biology. NUP98-X variants are not cryptic and are associated with WT1 mutations. Fusion partners also define immunophenotypic, transcriptomic, and epigenomic profiles. Importantly, NUP98 fusions predict poor overall survival, except for patients with abnormal chromosome 13.
Article
Oncology
Disha Malani, Ashwini Kumar, Oscar Bruck, Mika Kontro, Bhagwan Yadav, Monica Hellesoy, Heikki Kuusanmaki, Olli Dufva, Matti Kankainen, Samuli Eldfors, Swapnil Potdar, Jani Saarela, Laura Turunen, Alun Parsons, Imre Vastrik, Katja Kivinen, Janna Saarela, Riikka Raty, Minna Lehto, Maija Wolf, Bjorn Tore Gjertsen, Satu Mustjoki, Tero Aittokallio, Krister Wennerberg, Caroline A. Heckman, Olli Kallioniemi, Kimmo Porkka
Summary: Functional precision medicine tumor board integrates clinical, molecular, and functional data to guide treatment decisions for patients with acute myeloid leukemia. A high percentage of patients have actionable drugs identified, with a significant response rate to individually tailored therapies. Integration of data across patients enables the identification of drug response biomarkers for continuous improvement in personalized cancer medicine.
Article
Oncology
Suvi Kontro, Jani Raitanen, Kimmo Porkka, Anssi Auvinen
Summary: This study based on nationwide registry data shows that the incidence of myelodysplastic syndromes (MDS) in Finland is similar or slightly higher than in other Western countries, with an increasing trend followed by a decline towards the end of the study period.
Article
Hematology
Hartmut Doehner, Andrew H. Wei, Gail J. Roboz, Pau Montesinos, Felicitas R. Thol, Farhad Ravandi, Herve Dombret, Kimmo Porkka, Irwindeep Sandhu, Barry Skikne, Wendy L. See, Manuel Ugidos, Alberto Risueno, Esther T. Chan, Anjan Thakurta, C. L. Beach, Daniel Lopes de Menezes
Summary: The QUAZAR AML-001 trial evaluated the efficacy of oral azacitidine in patients with acute myeloid leukemia, showing improved relapse-free survival and overall survival, particularly in patients with NPM1(mut) and FLT3(mut).
Letter
Biophysics
Freja Ebeling, Johanna Illman, Matti Kankainen, Mika Kontro, Anu Partanen, Leila Sahlstedt, Mikko Myllymaki, Riitta Niittyvuopio, Soili Kytola
BONE MARROW TRANSPLANTATION
(2023)
Article
Biochemistry & Molecular Biology
Anniina Tervi, Nella Junna, Martin Broberg, Samuel E. Jones, Satu Strausz, Hanna-Riikka Kreivi, Caroline A. Heckman, Hanna M. Ollila, FinnGen
Summary: Tuberculosis is a significant public health concern that causes over 1 million deaths worldwide each year. This study identified specific HLA alleles and lifestyle risk factors, such as smoking, that are associated with the risk of tuberculosis.
HUMAN MOLECULAR GENETICS
(2023)
Letter
Hematology
Aarif M. N. Batcha, Nele Buckup, Stefanos A. Bamopoulos, Vindi Jurinovic, Maja Rothenberg-Thurley, Hanna Gittinger, Bianka Ksienzyk, Annika Dufour, Stephanie Schneider, Mika Kontro, Joseph Saad, Caroline A. Heckmann, Cristina Sauerland, Dennis Goerlich, Wolfgang E. Berdel, Bernhard J. Woermann, Utz Krug, Jan Braess, Ulrich Mansmann, Wolfgang Hiddermann, Karste Spiekermann, Klaus H. Mezeler, Tobias Herold
Summary: Although AML is primarily caused by somatic gene mutations, germline variants can also impact disease characteristics and patient outcomes. SNPs have been identified that are significantly associated with survival, therapy response, and other outcome variables in AML. However, SNPs are not yet included in routine risk assessment. This study aims to validate these SNPs in a large patient cohort and explore their potential prognostic role in commonly affected genes.
Article
Hematology
Heikki Kuusanmaki, Sari Kytola, Ida Vanttinen, Tanja Ruokoranta, Amanda Ranta, Jani Huuhtanen, Minna Suvela, Alun Parsons, Annasofia Holopainen, Anu Partanen, Milla E. L. Kuusisto, Sirpa Koskela, Riikka Raty, Maija Itala-Remes, Imre Vastrik, Olli Dufva, Sanna Siitonen, Kimmo Porkka, Krister Wennerberg, Caroline A. Heckman, Pia Ettala, Marja Pyorala, Johanna Rimpilainen, Timo Siitonen, Mika Kontro
Summary: The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. However, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored.
Article
Multidisciplinary Sciences
Benedicte Sjo Tislevoll, Monica Hellesoy, Oda Helen Eck Fagerholt, Stein-Erik Gullaksen, Aashish Srivastava, Even Birkeland, Dimitrios Kleftogiannis, Pilar Ayuda-Duran, Laure Piechaczyk, Dagim Shiferaw Tadele, Jorn Skavland, Baliakas Panagiotis, Randi Hovland, Vibeke Andresen, Ole Morten Seternes, Tor Henrik Anderson Tvedt, Nima Aghaeepour, Sonia Gavasso, Kimmo Porkka, Inge Jonassen, Yngvar Floisand, Jorrit Enserink, Nello Blaser, Bjorn Tore Gjertsen
Summary: In this study, the initial signaling response to standard induction chemotherapy in 32 acute myeloid leukemia (AML) patients was investigated using 36-dimensional mass cytometry. The reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy was found to be a significant predictor of patient 5-year overall survival in this cohort. This study demonstrates the value of mass cytometry in early response evaluation in AML and highlights the potential of functional signaling analyses in precision oncology diagnostics.
NATURE COMMUNICATIONS
(2023)
Letter
Hematology
Lok Lam Ngai, Diana Hanekamp, Fleur Janssen, Jannemieke Carbaat-Ham, Maaike A. M. A. Hofland, Mona M. H. E. Fayed, Angele Kelder, Laura Oudshoorn-van Marsbergen, Willemijn J. Scholten, Alexander N. Snel, Costa Bachas, Jesse M. Tettero, Dimitri A. Breems, Thomas Fischer, Bjorn T. Gjertsen, Laimonas Griskevicius, Gunnar Juliusson, Arjan A. van de Loosdrecht, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R. Passweg, Kimmo Porkka, Peter J. M. Valk, Patrycja Gradowska, Bob Lowenberg, David C. de Leeuw, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Jacqueline Cloos
Article
Oncology
Sini Luoma, Philipp Sergeev, Komal Kumar Javarappa, Tiina J. Ohman, Markku Varjosalo, Marjaana Saily, Pekka Anttila, Marja Sankelo, Anu Partanen, Anne Nihtinen, Caroline A. A. Heckman, Raija Silvennoinen
Summary: The bone marrow microenvironment plays a significant role in cancer survival and immune evasion in multiple myeloma (MM). By analyzing longitudinal bone marrow samples, researchers found distinct immune profiles between patients with good and bad responses to specific treatment. These findings suggest that deep immune profiling could be a useful tool for treatment guidance and require further investigation.
Article
Oncology
Johanna Vikkula, Kristiina Uusi-Rauva, Tuuli Ranki, Iiro Toppila, Maria Aalto-Setala, Katariina Pousar, Lotta Vassilev, Kimmo Porkka, Raija Silvennoinen, Oscar Bruck
Summary: This study analyzed data from 509 adult MM patients and found that treatment pattern diversity increased with improved access to novel treatments. For patients eligible for stem cell transplantation, high first-year hospitalization costs were followed by stable resource requirements.
Article
Biochemistry & Molecular Biology
Angeliki Katsenou, Roisin O'Farrell, Paul Dowling, Caroline A. Heckman, Peter O'Gorman, Despina Bazou
Summary: This paper presents a machine learning decision support system that provides a list of chemotherapeutics for multiple myeloma patients based on their proteomic profile. The results indicate that utilizing proteomics data shows promise in identifying effective treatment options for MM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Oncology
Alisa Olkinuora, Taina T. Nieminen, Suvi Douglas, Anni Kauppinen, Mika Kontro, Juho Vaananen, Matti Kankainen, Ari Ristimaki, Markus Makinen, Paivi Lahermo, Caroline Heckman, Janna Saarela, Milla Salonen, Anna Lepisto, Heikki Jarvinen, Jukka-Pekka Mecklin, Outi Kilpivaara, Ulla Wartiovaara-Kautto, Kimmo Porkka, Paeivi Peltomaki
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)
