The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK(wt), TEL-SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK(wt) enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK-SYK caused lethal T-cell lymphomas and the cytoplasmic TEL-SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL-SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL-SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL-SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219468 | PMC |
| http://dx.doi.org/10.1038/bcj.2014.53 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PET-CT-based host metabolic (PETMet) features are associated with pathologic response in gastroesophageal adenocarcinoma.
Eur J Surg Oncol
January 2025
Division of Surgical Oncology, Department of Surgery, Northwell Health, New Hyde Park, NY, USA; Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:
Background: F-FDG PET-CT-based host metabolic (PETMet) profiling of non-tumor tissue is a novel approach to incorporate the patient-specific response to cancer into clinical algorithms.
Materials And Methods: A prospectively maintained institutional database of gastroesophageal cancer patients was queried for pretreatment PET-CTs, demographics, and clinicopathologic variables. F-FDG PET avidity was measured in 9 non-tumor tissue types (liver, spleen, 4 muscles, 3 fat locations).
A comparative study of the genetically improved Abbassa Nile tilapia strain (GIANT-G9) and a commercial strain in Egypt: growth vs. stress response.
Vet Res Commun
January 2025
Genetics and Biotechnology, Department of Aquaculture, Faculty of Fish Resources, Suez University, Suez, 43221, Egypt.
Selective breeding is a potent method for developing strains with enhanced traits. This study compared the growth performance and stress responses of the genetically improved Abbassa Nile tilapia strain (G9; GIANT-G9) with a local commercial strain over 12 weeks, followed by exposure to stressors including high ammonia (10 mg TAN/L), elevated temperature (37 °C), and both for three days. The GIANT-G9 showed superior growth, including greater weight gain, final weight, length gain, specific growth rate, and protein efficiency ratio, as well as a lower feed conversion ratio and condition factor compared to the commercial strain.
View Article and Find Full Text PDFMolecular characterization and phylogenetic analysis of African swine fever virus from a pig farm in India.
Vet Res Forum
November 2024
Department of Veterinary Medicine, College of Veterinary and Animal Sciences, Sardar Vallabhbhai Patel University of Agriculture and Technology, Meerut, India.
African swine fever (ASF) is considered as one of the most threatening diseases for the pig farming industry all over the world. Due to the lack of an effective vaccine, organized farms and backyard rearing must strictly enforce control measures in order to combat the disease. The present report describes the ASF epidemic in a piggery in Uttar Pradesh state, India.
View Article and Find Full Text PDFTherapeutic efficacy of against phenylhydrazine-induced hemolytic anemia in rats.
J Tradit Complement Med
January 2025
School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, India.
Background & Aim: Hemolytic anemia is a blood disorder whose incidence is increasing in the world in recent years especially after the pandemic. Conventional treatments include use of steroids and immunosuppresants that are accompanied by numerous adverse effects. With growing interest in using complex multi-component formulations for multi-targeted therapy, the present study aims to investigate the therapeutic efficacy of a traditional herbomineral preparation, , which has been traditionally used as a supplement in iron-deficiency anemia, against phenylhydrazine-induced hemolytic anemia in rodent models.
View Article and Find Full Text PDFTraditional Chinese Medicine for Liver Cancer Treatment: Network Pharmacology Research.
Curr Top Med Chem
January 2025
Shangzhuang Township Community Health Service Center, Beijing, 100094, China.
Background: As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!