Article
Pharmacology & Pharmacy
Kyung-Sook Chung, Chae-Bin Yoo, Jeong-Hun Lee, Hwi-Ho Lee, Sang-Eun Park, Hee-Soo Han, Su-Yeon Lee, Byoung-Mok Kwon, Jung-Hye Choi, Kyung-Tae Lee
Summary: The study shows that 2'-HCA induces apoptosis in HL-60 cells via activation of the ROS-dependent JNK pathway, suggesting its potential as a therapeutic agent for leukemia.
Editorial Material
Hematology
Qian-Fei Wang, Hong -Hu Zhu
Summary: In this study, Poplineau et al identified a retinoic acid resistance network involving the E2F-EZH2 axis in a PLZF-RARA transgenic acute promyelocytic leukemia mouse model. They demonstrated that the nonenzymatic activity of EZH2 is crucial for retinoic acid resistance. Targeting the pan-EZH2 activity significantly improved survival in mice reconstituted with retinoic acid-resistant PLZF-RARA leukemia cells.
Review
Cell Biology
Mojdeh Barati, Behrad Darvishi, Mohammad Amin Javidi, Ali Mohammadian, Seyed Peyman Shariatpanahi, Mohammad Reza Eisavand, Alireza Madjid Ansari
Summary: The induction of apoptosis in exposed cells by ELF-EMF is controversial, with studies showing conflicting results. The cellular stress response following ELF-EMF exposure may play a critical role in modulating apoptotic effects, highlighting the key factor influencing discrepancies in observations.
CELL PROLIFERATION
(2021)
Article
Oncology
Leo Ruhnke, Friedrich Stoelzel, Lisa Wagenfuehr, Heidi Altmann, Uwe Platzbecker, Sylvia Herold, Andreas Rump, Evelin Schroeck, Martin Bornhaeuser, Johannes Schetelig, Malte von Bonin
Summary: Patients with acute promyelocytic leukemia (APL) often have life-threatening hemorrhagic diathesis due to complex pathomechanisms. Non-APL acute myeloid leukemia (AML) patients may also be at risk of severe coagulopathy, as demonstrated by a case study showing expression of the APL-specific biomarker ANXA2 in a non-APL AML patient's bone marrow cells. Further research is needed to understand the regulation of ANXA2 and assess its potential as a marker for risk of disseminated intravascular coagulation in AML and APL patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xuejing Shao, Yingqian Chen, Aixiao Xu, Danyan Xiang, Wei Wang, Wenxin Du, Yunpeng Huang, Xingya Zhang, Minyi Cai, Zhimei Xia, Yi Wang, Ji Cao, Yan Zhang, Bo Yang, Qiaojun He, Meidan Ying
Summary: Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML/RAR alpha, which disrupts the construction of PML nuclear bodies (NBs). The disrupted NB assembly in APL is caused by neddylation-induced aberrant phase separation of PML/RAR alpha. Deneddylation restores the phase separation process, suppresses leukemogenesis, and can be targeted for APL eradication.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Medicine, General & Internal
Xuehui Zhou, Chengwen Li
Summary: This case report highlights the rare occurrence of recurrent GS in an APL patient in complete remission for 24 years, with excellent responses to ATRA, chemotherapy, and ATO, ultimately achieving complete remission.
Review
Oncology
Uday Kulkarni, Vikram Mathews
Summary: Treatment for acute promyelocytic leukemia has transformed from being the most malignant form of acute leukemia to one with excellent long term survival rates over the past three decades. Current treatment regimens for APL incorporate minimal chemotherapeutic drugs, with a potential future shift towards completely oral arsenic trioxide + ATRA regimen for low-intermediate risk cases. For high-risk cases, minimal anthracycline use with ATO + ATRA might become the standard of care soon. Promising non-chemotherapy drugs are being explored for high risk and relapsed cases, with a potential to translate to a complete oral chemotherapy free combination regimen in the future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xibao Yu, Xin Liu, Xuan Liu, Shuang Jin, Mengjun Zhong, Dingrui Nie, Xiangbo Zeng, Xianfeng Wang, Jiaxiong Tan, Yangqiu Li, Chengwu Zeng
Summary: CASP1/GSDMD expression is lower in patients with acute promyelocytic leukemia (APL) and most other subtypes of primary de novo acute myeloid leukemia (AML), but is increased in all-trans-retinoic acid (ATRA)-treated APL cells; ATRA induces CASP1 expression via the IFN gamma/STAT1 pathway and triggers pyroptotic cell death and differentiation in APL cells, serving as a suppressor in APL progression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Hematology
Siyuan Xu, Siqing Wang, Shenghui Xing, Dingdang Yu, Bowen Rong, Hai Gao, Mengyao Sheng, Yun Tan, Xiaojian Sun, Kankan Wang, Kai Xue, Zhennan Shi, Fei Lan
Summary: Epigenetic abnormalities play a critical role in cancer, specifically in diseases like AML where aberrant fusion proteins drive the disease. The loss of KDM5A leads to differentiation and growth retardation in APL NB4 cells, by suppressing the expression of key target genes. Inhibition of KDMSA could greatly enhance differentiation in NB4 cells, suggesting a potential therapeutic target in APL treatment.
Article
Multidisciplinary Sciences
William Villiers, Audrey Kelly, Xiaohan He, James Kaufman-Cook, Abdurrahman Elbasir, Halima Bensmail, Paul Lavender, Richard Dillon, Borbala Mifsud, Cameron S. Osborne
Summary: The PML-RARA gene fusion is the characteristic driver of Acute Promyelocytic Leukaemia (APL) and is known to bind to the genome. Here, the authors characterise the impact of PML-RARA on gene regulation in APL cell lines and patient samples using transcriptomics, epigenomics, and machine learning.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Serena Rosati, Carmelo Gurnari, Massimo Breccia, Ida Carmosino, Emilia Scalzulli, Enrico Montefusco, Salvatore Perrone, Ombretta Annibali, Vincenza Martini, Giulio Trape, Gioia Colafigli, Malgorzata Trawinska, Clara Minotti, Giuseppe Cimino, Agostino Tafuri, Giuseppe Avvisati, Maurizio Martelli, Maria Teresa Voso, Roberto Latagliata
Summary: The study found that nearly half of older APL patients aged 70 and above received sub-optimal induction treatments, leading to dismal outcomes. This highlights the importance of adopting standard therapies instead of modified or reduced personalized approaches in the setting of frail older patients.
Article
Oncology
Alexandra Ghiaur, Cristina Doran, Bogdan Ionescu, Lacramioara -Andreea Mohorea-Neata, Camelia Stancioaica, Roxana Hirjan, Aurelia Tatic, Mihaela Cirstea, Didona Vasilache, Dana Tabac, Ioana Lupescu, Daniel Coriu
Summary: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia that is highly curable. However, it is associated with high early mortality rates due to complications such as coagulopathy, differentiation syndrome, and infectious events. The COVID-19 pandemic has further complicated the management of APL patients, as they are at higher risk of severe complications and poor outcomes.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Hui He, Chengqiang Wang, Gen Liu, Haoyue Ma, Mingdong Jiang, Pan Li, Qianwei Lu, Li Li, Hongyi Qi
Summary: The study demonstrates that Isobavachalcone induces apoptosis and differentiation of acute myeloid leukemia cells through multiple pathways, with the ROS-mediated signaling pathway playing a key role.
PHYTOTHERAPY RESEARCH
(2021)
Article
Oncology
Matteo Molica, Carla Mazzone, Tiziana Ottone, Pasquale Niscola, Elisabetta Abruzzese, Stefano Fratoni, Maria Teresa Voso, Paolo de Fabritiis
Summary: Relapses of acute promyelocytic leukemia (APL) beyond 7 years from the first molecular remission are rare, and it is unclear whether these relapses represent a therapy-related leukemia or a delayed relapse of the original leukemic clone. The increase in extra-medullary relapses (ER) in the era of all-trans retinoic acid (ATRA) therapy suggests a potential correlation between ATRA therapy and ER, and the optimal post-remission approach for late relapse patients remains to be established.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christina M. Wolff, Juergen F. Kolb, Sander Bekeschus
Summary: In modern oncology, combining different therapies to enhance treatment efficacy is a common approach. The combination of microsecond-pulsed electric fields and cold physical plasma treatment has shown synergistic effects, increasing the accumulation of reactive oxygen species (ROS), enhancing cytotoxicity against cancer cells, and promoting immune responses.
Review
Oncology
Stefano Amatori, Simona Tavolaro, Stefano Gambardella, Mirco Fanelli
Summary: The oncogenic role of histone mutations has been identified in various types of tumors, with mutations targeting both N-terminal tails and globular histone fold domains. Oncohistones are often dominant-negative and more prevalent in tumors affecting children and adolescents. Further studies are needed to understand the mechanisms of action of oncohistones and their potential application in cancer classification and treatment.
CLINICAL EPIGENETICS
(2021)
Article
Genetics & Heredity
Rosa Campopiano, Cinzia Femiano, Maria Antonietta Chiaravalloti, Rosangela Ferese, Diego Centonze, Fabio Buttari, Stefania Zampatti, Mirco Fanelli, Stefano Amatori, Carmelo D'Alessio, Emiliano Giardina, Francesco Fornai, Francesca Biagioni, Marianna Storto, Stefano Gambardella
Summary: X-linked adrenoleukodystrophy (X-ALD) is a commonly seen peroxisomal disorder caused by defects in the ABCD1 gene, leading to VLCFAs accumulation, even in female carriers.
Review
Biochemistry & Molecular Biology
Stefano Amatori, Mirco Fanelli
Summary: Epigenomic aberrations in cancer cells play a role in cancer initiation and progression. Formalin fixation and paraffin embedding (FFPE) is widely used to preserve tissue integrity, and new chromatin immunoprecipitation (ChIP) techniques allow analysis of histone post-translational modifications and transcription factor distribution in FFPE tissues. However, the variability in fixation and storage conditions of clinical specimens can affect the success of ChIP studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Giuseppe Persico, Francesca Casciaro, Stefano Amatori, Martina Rusin, Francesco Cantatore, Amalia Perna, Lavinia Alberi Auber, Mirco Fanelli, Marco Giorgio
Summary: This study discovered specific markers of histone modifications in Alzheimer's disease patients, confirming the role of epigenetic chromatin remodeling in neurodegenerative diseases and shedding light on the genomic regulatory mechanisms involved in Alzheimer's disease.
Letter
Genetics & Heredity
Rosangela Ferese, Simona Scala, Antonio Suppa, Rosa Campopiano, Francesco Asci, Maria Antonietta Chiaravalloti, Alessandro Zampogna, Carmelo D'Alessio, Filomena Fittipaldi, Fabio Buttari, Alba Di Pardo, Emiliano Giardina, Stefania Zampatti, Francesco Fornai, Giuseppe Novelli, Mirco Fanelli, Chiara Zecca, Giancarlo Logroscino, Diego Centonze, Stefano Gambardella
Summary: The flowchart presents the molecular approach employed for decoding non-canonical splicing mutations.
Article
Biotechnology & Applied Microbiology
Stefano Amatori, Giuseppe Persico, Francesco Cantatore, Martina Rusin, Mauro Formica, Luca Giorgi, Eleonora Macedi, Francesca Casciaro, Alfredo Errico Provenzano, Stefano Gambardella, Roberta Noberini, Tiziana Bonaldi, Vieri Fusi, Marco Giorgio, Mirco Fanelli
Summary: This study characterizes the epigenomic effects of maltonis, a novel maltol-derived molecule, in acute promyelocytic leukemia (APL) cells. The results show that maltonis treatment can remodel histone code, alter gene expression, induce an antiviral-like response, and regulate c-MYC-related pathways.
CANCER GENE THERAPY
(2023)
Article
Cell Biology
Roman Hillje, Lucilla Luzi, Stefano Amatori, Giuseppe Persico, Francesca Casciaro, Martina Rusin, Mirco Fanelli, Piergiuseppe Pelicci, Marco Giorgio
Summary: By comparing the age profiles of histone H3 modifications in the livers of healthy mice, we observed a global redistribution of histone H3 modifications with time, especially in intergenic regions and near transcription start sites, as well as changes in the correlation between different histone modifications. Additionally, we found that caloric restriction diet can reduce the extent of these changes.
Article
Genetics & Heredity
Francesca Casciaro, Giuseppe Persico, Martina Rusin, Stefano Amatori, Claire Montgomery, Jennifer R. Rutkowsky, Jon J. Ramsey, Gino Cortopassi, Mirco Fanelli, Marco Giorgio
Summary: The study found that histone H3 modifications in brain tissue during the progression of Alzheimer's disease are slightly affected by sex, while a higher number of differences are found in gastrocnemius muscles.
Article
Chemistry, Multidisciplinary
Luca Giorgi, Gianluca Ambrosi, Daniele Paderni, Luca Conti, Stefano Amatori, Francesca Romagnoli, Patrizia Rossi, Mauro Formica, Eleonora Macedi, Claudia Giorgi, Paola Paoli, Mirco Fanelli, Vieri Fusi
Summary: Two new maltol-based ligands, L1 and L2, were designed and studied to investigate their anticancer properties and metal coordination abilities. The introduction of methyl or hydroxymethyl function at C6 affected the degradation time and binding properties towards Cu(ii), Zn(ii), and Co(ii). The -CH2OH substitution at C6 was found to impair the biological activity of the compound, consistent with the hypothesized mechanism of action.
NEW JOURNAL OF CHEMISTRY
(2021)
