Von Hippel-Lindau disease (VHL disease) is a hereditary cancer predisposition syndrome caused by mutations of the von Hippel-Lindau tumor suppressor gene. The gene product, pVHL, regulates the level of proteins that play a central role in protecting cells against hypoxia. Clinical hallmarks of von Hippel-Lindau disease are the development of central nervous system hemangioblastomas, renal cell carcinoma, pheochromocytoma, neuroendocrine tumors and endolymphatic sac tumors.In this article the case of a 38-year old hemodialyzed patient who became ill with acute myeloid leukemia (AML) three years after being diagnosed with von Hippel-Lindau disease is presented.After cytostatic treatment the patient went into complete hematologic remission but there was still residual disease at the genetic level. After consolidation therapy patient developed bone marrow aplasia and severe pneumonia. Despite intensive treatment the patient died from acute respiratory failure.In this paper we present for the first time a case of von Hippel-Lindau disease associated with acute myeloid leukemia. No evidence of relationship between VHL disease and blood cancers has been demonstrated so far. Despite the fact that there is an increased risk of cancer development in hemodialyzed patients, cancer is a relatively rare cause of death in the dialysed population, and the most common malignancies are genitourinary cancers. It seems likely that development of acute myeloid leukemia in patient with VHL disease can be related to epigenetic alterations of the VHL gene, but further studies are needed.
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http://dx.doi.org/10.1186/1897-4287-11-11 | DOI Listing |
Genes (Basel)
December 2024
Department of Health Science, University of Florence, 50134 Florence, Italy.
Mutations of the von Hippel-Lindau () tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes.
View Article and Find Full Text PDFJ Kidney Cancer VHL
December 2024
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Central nervous system hemangioblastoma (CNS-HB) is the most common manifestation of von Hippel-Lindau disease (VHL). The main axis of the CNS-HB pathway is the VHL-HIF signaling pathway. Recently, we proposed an alternative VHL-JAK-STAT pathway in CNS-HB.
View Article and Find Full Text PDFClin Neurol Neurosurg
January 2025
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing 100070, China.
Purpose: Hemangioblastomas (HBs) occurring in the cervical spinal region are infrequently reported. Surgical resection of cervical HBs poses a significant challenge, and the long-term therapeutic outcomes remain unclear.
Methods: A comprehensive retrospective analysis was conducted to review the treatment outcomes of patients with cervical HBs from 2011 to 2021.
Expert Opin Ther Pat
January 2025
Centre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee, UK.
Introduction: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012).
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
January 2025
Technical University of Darmstadt, Clemens-Schöpf Institute of Organic Chemistry and Biochemistry, Department of Chemistry, Peter-Grünberg-Straße 4, 64287 Darmstadt, Germany.
Molecular glues (MGs) and proteolysis-targeting chimeras (PROTACs) are used to modulate protein-protein interactions (PPIs), via induced proximity between compounds that have little or no affinity for each other naturally. They promote either reversible inhibition or selective degradation of a target protein, including ones deemed undruggable by traditional therapeutics. Though native MS (nMS) is capable of analyzing multiprotein complexes, the behavior of these artificially induced compounds in the gas phase is still not fully understood, and the number of publications over the past few years is still rather limited.
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