Editorial Material
Hematology
Carol Fries, Michelle L. Hermiston
Summary: In this issue of Blood, Courtois et al. identified interleukin-7 receptor (IL-7R) expression as a potential biomarker for predicting sensitivity to JAK pathway inhibition in T-cell acute lymphoblastic leukemia (T-ALL).
Article
Medicine, Research & Experimental
Yuqian Chang, Pan Kang, Tingting Cui, Weinan Guo, Weigang Zhang, Pengran Du, Xiuli Yi, Sen Guo, Tianwen Gao, Chunying Li, Shuli Li
Summary: T-96, extracted from Tripterygium wilfordii Hook F, has been found to have anti-inflammatory and immunosuppressive properties. It can effectively inhibit the activation and infiltration of CD8(+) T cells in the skin, making it a potential therapeutic option for vitiligo.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Georgiana Toma, Ioana Maria Lemnian, Eliza Karapetian, Ivo Grosse, Barbara Seliger
Summary: Memory CD8(+) T cells increase with aging, leading to higher susceptibility to infections and decreased vaccine efficiency. In this study, the age-dependent expression profile of CD8(+) T cells from young and old donors was analyzed. The results showed that CD8(+)CD45RA(-) memory T cells from old donors maintained the characteristics of total CD8(+) T cells, including increased cytokine secretion and JAK-STAT pathway transcripts.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Farah Khashab, Farah Al-Saleh, Nora Al-Kandari, Fatemah Fadel, May Al-Maghrebi
Summary: The study establishes a direct link between JAK2 activation and DNA damage response signaling pathways in testicular ischemia reperfusion injury. Inhibition of JAK2 activity by AG490 prevents oxidative DNA damage and activation of apoptosis pathways, highlighting the role of JAK2 in regulating germ cell apoptosis in tIRI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yuriko Kinoshita, Naoka Shiratsuchi, Mayo Araki, Yoshihiro H. Inoue
Summary: Several antimicrobial peptides can suppress the growth of lymph gland tumors in Drosophila mutant larvae, while the effects of Turandot proteins on Drosophila tumors are not clear. The JAK/STAT pathway is activated in the tumors and other tissues of mutant larvae. Turandot genes are upregulated in the mutant fat body and their expression is dependent on the JAK/STAT pathway. Silencing of these genes in the fat body enhances tumor growth, suggesting their antitumor effects. Moreover, the proteins are found to be incorporated into small vesicles in mutant circulating hemocytes and more hemocytes containing these proteins are associated with tumors.
Review
Pharmacology & Pharmacy
Hong-Tai Tzeng, I-Tsu Chyuan, Jenn-Haung Lai
Summary: The JAK/STAT signaling pathway plays a crucial role in immune regulation, affecting cell proliferation, survival, inflammation, and immune tolerance. Aberrant activation of this pathway can lead to autoimmune diseases and cancer progression, while targeting JAK/STAT has shown efficacy in suppressing inflammation. The success of small-molecule JAK inhibitors in treating rheumatologic diseases highlights their therapeutic potential in other conditions.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Cell Biology
Bhawana Maurya, Satya Surabhi, Rituparna Das, Pranjali Pandey, Ashim Mukherjee, Mousumi Mutsuddi
Summary: Mahe, an RNA helicase, regulates Notch signaling and neuronal development in Drosophila. The study demonstrates that Mahe can promote apoptosis by modulating the JAK/STAT pathway components. Through transcriptome profiling and RNA immunoprecipitation experiments, the study reveals the regulatory mechanism of Mahe on the JAK/STAT pathway.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Charlotte Mallart, Fabienne Chalvet, Sophie Netter, Alba Yurani Torres, Mickael Poidevin, Jacques Montagne, Anne-Marie Pret, Marianne Malartre
Summary: The JAK-STAT pathway plays an important role in Drosophila, but its regulation mechanism is not fully understood. This study discovered that JAK-STAT signaling displays dynamic asymmetry during Drosophila oogenesis, similar to the accumulation of the adherens junction protein E-cadherin. The study also revealed the critical role of E-cadherin in regulating JAK-STAT activity throughout oogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Plant Sciences
Jinsong Su, Qiuyue Li, Jia Liu, Hongling Wang, Xuanhao Li, Dhondrup Wuentrang, Chuan Liu, Qian Zhao, Ruyu Yao, Xianli Meng, Yi Zhang
Summary: The study aimed to explore the anti-rheumatoid arthritis (RA) effect and mechanism of Rhamnella gilgitica extract on collagen-induced arthritis (CIA) in rats. Results showed that RGEA promoted apoptosis, inhibited inflammation, and regulated the JAK-STAT pathway, contributing to its anti-RA effect.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Review
Immunology
Maddison Lensing, Ali Jabbari
Summary: Alopecia Areata (AA) is a common autoimmune disease characterized by hair loss. The breakdown of immune privilege of the hair follicle plays a role in the development of the disease. IFN gamma and other cytokines are involved in the pathogenesis of AA. Targeting the JAK/STAT signaling pathways has been shown to be effective in treating the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Aikaterini Tsiogka, Maria Kyriazopoulou, George Kontochristopoulos, Electra Nicolaidou, Alexander Stratigos, Dimitris Rigopoulos, Stamatios Gregoriou
Summary: In recent years, the understanding of the pathogenesis of atopic dermatitis (AD) has expanded, leading to the development of novel therapeutic molecules that target the core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway is involved in intracellular signal transduction and gene transcription regulation. The activation of T-helper (Th)-2 and Th22 immune responses plays a pivotal role in the immunopathogenesis of AD, followed by a variable degree of Th1 and Th17 activation. JAK inhibitors have emerged as a potential treatment option for AD due to their ability to inhibit the signal transduction of inflammatory cytokines.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Plant Sciences
Maria Rosaria Perri, Michele Pellegrino, Stefano Aquaro, Fabiola Cavaliere, Carmine Lupia, Dimitar Uzunov, Mariangela Marrelli, Filomena Conforti, Giancarlo Statti
Summary: The study investigated the phytochemical profile and anti-inflammatory properties of three Cachrys species from Southern Italy. The extracts were found to be rich in furanocoumarins, with potential for inhibiting the JAK/STAT signaling pathway and reducing pro-inflammatory cytokines and mediators.
Article
Hematology
Antonio Lahera, Pilar Lopez-Nieva, Hernan Alarcon, Jose L. Marin-Rubio, Maria A. Cobos-Fernandez, Pablo Fernandez-Navarro, Agustin F. Fernandez, Laura Vela-Martin, Isabel Sastre, Sara Ruiz-Garcia, Pilar Llamas, Jose L. Lopez-Lorenzo, Javier Cornago, Javier Santos, Jose Fernandez-Piqueras, Maria Villa-Morales
Summary: Despite frequent alterations in the JAK/STAT pathway in T-ALL/LBL, there is currently no approved therapy for patients with constitutive JAK/STAT signaling. This study identifies SOCS3 hypermethylation as a recurrent event in T-ALL/LBL and demonstrates its potential as a therapeutic target by counteracting the constitutive activation of the JAK/STAT pathway through different molecular mechanisms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Minhao Chen, Longfei Xiao, Guangchun Dai, Panpan Lu, Yuanwei Zhang, Yingjuan Li, Ming Ni, Yunfeng Rui
Summary: Aging leads to an accumulation of senescent TSPCs in tendon tissue, with an increase in the activity of the JAK-STAT signaling pathway. Genetic knockdown of JAK2 or STAT3 significantly reduces cellular senescence in aged TSPCs. Pharmacological inhibition of JAK-STAT signaling pathway with AG490 also alleviates cellular senescence and age-related dysfunctions in TSPCs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Qianqian Yin, Longyun Wang, Haiyang Yu, Daquan Chen, Wenwei Zhu, Changgang Sun
Summary: The JAK-STAT signaling pathway is closely related to cell proliferation, apoptosis, differentiation, and inflammatory response, essential for inhibiting inflammation, initiating innate immunity, and coordinating adaptive immune mechanisms. Various plant polyphenol compounds play a role in suppressing abnormal activation in the JAK-STAT pathway, showing significant effects in anti-inflammatory, antitumor, and cardiovascular disease control.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Alise K. Murray, Rose B. McGee, Roya M. Mostafavi, Xiaoqing Wang, Zhaohua Lu, Jessica M. Valdez, Michael A. Terao, Kim E. Nichols
Summary: The survey revealed that most PHO physicians and fellows believe that understanding tumor and germline genomic information is essential for their practice, but only a few programs have an existing cancer genomics curriculum. The majority of program directors indicated that the ideal genomics curriculum should occur during the first year of fellowship and incorporate direct patient care, online modules, and problem-based learning.
Letter
Hematology
Marta Salek, Ninad Oak, Melissa Hines, Jamie L. Maciaszek, Ruth Tatevossian, Akshay Sharma, Kim E. Nichols, Patrick Campbell
Article
Oncology
David T. Teachey, Meenakshi Devidas, Brent L. Wood, Zhiguo Chen, Robert J. Hayashi, Michelle L. Hermiston, Robert D. Annett, J. Hunter Archer, Barbara L. Asselin, Keith J. August, Steve Y. Cho, Kimberly P. Dunsmore, Brian T. Fisher, Jason L. Freedman, Paul J. Galardy, Paul Harker-Murray, Terzah M. Horton, Alok Jaju, Allison Lam, Yoav H. Messinger, Rodney R. Miles, Maki Okada, Samir Patel, Eric S. Schafer, Tal Schechter, Neelam Singh, Amii C. Steele, Maria Luisa Sulis, Sarah L. Vargas, Stuart S. Winter, Charlotte Wood, Patrick Zweidler-McKay, Catherine M. Bollard, Mignon L. Loh, Stephen P. Hunger, Elizabeth A. Raetz
Summary: The study indicates that the use of proteasome inhibitor bortezomib can significantly improve event-free survival and overall survival in patients with T-LL. Additionally, intensification of systemic therapy allows for a reduction in the proportion of T-ALL patients requiring prophylactic cranial radiation without increasing the risk of relapse.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Suzanne P. MacFarland, Luke Maese, Surya P. Rednam, Junne Kamihara, Melissa R. Perrino, Kim E. Nichols, Garrett M. Brodeur, Joshua D. Schiffman, Sharon E. Plon, Lisa R. Diller, David Malkin, Christopher C. Porter, Anita Villani
Summary: Germline pathogenic variants are frequently found in children with cancer. Due to the rarity and underrecognition of pediatric cancer predisposition syndromes, a new consortium has been established to optimize care and advance research in this area.
CANCER PREVENTION RESEARCH
(2022)
Article
Biology
Eda R. Machado, Diantha van de Vlekkert, Heather S. Sheppard, Scott Perry, Susanna M. Downing, Jonathan Laxton, Richard Ashmun, David B. Finkelstein, Geoffrey A. Neale, Huimin Hu, Frank C. Harwood, Selene C. Koo, Gerard C. Grosveld, Alessandra D'Azzo
Summary: A mouse model of pleomorphic rhabdomyosarcoma, driven by haploinsufficiency of neuraminidase 1, provides a useful tool for diagnostic and therapeutic studies. The model displays features of embryonal and alveolar rhabdomyosarcoma and is characterized by increased lysosomal exocytosis and the presence of partially differentiated cells. These findings, along with the identification of an adipogenic signature, make this model ideal for further research.
COMMUNICATIONS BIOLOGY
(2022)
Article
Hematology
William C. Temple, Stephanie Mueller, Michelle L. Hermiston, Birgit Burkhardt
Summary: Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin Lymphoma (NHL) in children, adolescents, and young adults, with T-lymphoblastic lymphoma (T-LBL) accounting for 70-80% of cases and precursor B-lymphoblastic lymphoma (pB-LBL) accounting for the remaining 20-25% of cases. The current treatment has shown good overall prognosis, but relapsed or refractory (r/r) disease remains a challenge. This review focuses on the pathogenesis, clinical results, and future directions for therapy in LBL.
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
(2023)
Review
Hematology
Stephanie J. Si Lim, James B. Ford, Michelle L. Hermiston
Summary: T-cell lymphoblastic lymphoma (T-LLy) and T-cell acute lymphoblastic leukemia (T-ALL) were historically considered as variations of the same disease. However, recent evidence suggests that they may be distinct clinical and biological entities due to differential responses to chemotherapy. This article examines the differences between T-LLy and T-ALL, provides recommendations on the treatment of newly diagnosed and relapsed/refractory T-LLy patients, and discusses ongoing investigations into novel therapies and the role of stem cell transplantation.
Article
Genetics & Heredity
Leora Witkowski, Kim E. Nichols, Marjolijn Jongmans, Nienke van Engelen, Ronald R. de Krijger, Jennifer Herrera-Mullar, Lieve Tytgat, Armita Bahrami, Helen Mar Fan, Aimee L. Davidson, Thomas Robertson, Michael Anderson, Martin Hasselblatt, Sharon E. Plon, William D. Foulkes
Summary: Heterozygous germline pathogenic variants in the SMARCA4 gene can predispose to several rare tumour types, including neuroblastoma. These findings suggest that neuroblastoma should be included in the spectrum of SMARCA4-associated tumours.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Margaret B. B. Nagel, Melissa R. R. Perrino, Regina Nuccio, Alise K. K. Blake, Lynn Harrison, Kim E. E. Nichols, Alberto S. S. Pappo
Summary: In this retrospective study, the prevalence and spectrum of germline variants in cancer predisposition genes were examined in 38 children and young adults with melanocytic lesions at St. Jude Children's Research Hospital. The study found that 15.8% of patients had pathogenic germline variants, including various genetic mutations in genes such as PMS2, TP53, BRIP1, ATM, and AXIN2.
PEDIATRIC BLOOD & CANCER
(2023)
Editorial Material
Hematology
Carol Fries, Michelle L. Hermiston
Summary: In this issue of Blood, Courtois et al. identified interleukin-7 receptor (IL-7R) expression as a potential biomarker for predicting sensitivity to JAK pathway inhibition in T-cell acute lymphoblastic leukemia (T-ALL).
Editorial Material
Hematology
Lauren K. Meyer, Kim E. Nichols
Summary: In this article, the authors present a novel in vitro approach to study germline variants in genes associated with familial hemophagocytic lymphohistiocytosis (fHLH). This method enables the analysis of variants of uncertain significance (VUS) and provides insights into their functional consequences.
Article
Oncology
Savannah S. Shumock, William C. Temple, Amanda Marinoff, Kathryn Aaronson, Erica Southworth, Simayijiang Xirenayi, Alex G. Lee, Stanley G. Leung, E. Alejandro Sweet-Cordero, Michelle Hermiston, Christine Higham, Elliot Stieglitz
Summary: This study reveals the potential application of TKIs in Ph-like B-ALL patients, especially pre- and post-HSCT. The case series data suggest that the combination of TKIs with chemotherapy or immunotherapy may be an effective strategy.
Article
Oncology
Belinda N. Mandrell, Liza Marie Johnson, Mary Caples, Jami Gattuso, Jamie L. Maciaszek, Roya Mostafavi, Katianne M. Howard Sharp, Kim E. Nichols
Summary: This study aimed to understand parent preferences regarding the timing and content of consent conversations for clinical germline genetic testing of children with cancer. The survey results revealed that most parents preferred consent conversations to take place one month after the cancer diagnosis and desired testing of as many cancer-related genes as possible.
JCO PRECISION ONCOLOGY
(2022)
Article
Psychology, Clinical
Holly M. Hasler, Alise Murray, Kristin E. Canavera, Kendra R. Parris, Kim E. Nichols, Lisa M. Jacola
Summary: This study found that individuals with PTEN hamartoma tumor syndrome (PHTS) commonly experience cognitive difficulties, including borderline to average global intellectual functioning and deficits in non-verbal reasoning, visual-motor integration, math achievement, and adaptive skills. Therefore, routine neurocognitive assessment should be considered in the management of PHTS patients.
JOURNAL OF PEDIATRIC NEUROPSYCHOLOGY
(2022)
Article
Hematology
Yixin Hu, Kenneth J. Caldwell, Mihaela Onciu, Sara M. Federico, Marta Salek, Sara Lewis, Shaohua Lei, Jinghui Zhang, Kim E. Nichols, Clifford M. Takemoto, Brandon M. Triplett, Jason E. Farrar, Jeffrey E. Rubnitz, Raul C. Ribeiro, Marcin W. Wlodarski
Summary: CP X-351, a fixed ratio of liposomal cytarabine to daunorubicin, is effective and well-tolerated in pediatric sMDS/AML patients, showing complete morphologic remission without significant toxicity. Prospective studies are warranted to further evaluate its potential in this population.