1. Myeloproliferative Neoplasms: Diseases Mediated by Chronic Activation of Signal Transducer and Activator of Transcription (STAT) Proteins.
- Author
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Liongue, Clifford and Ward, Alister C.
- Subjects
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STAT proteins , *PROTEINS , *GENETIC mutation , *CHRONIC myeloid leukemia , *MYELOPROLIFERATIVE neoplasms , *CELLULAR signal transduction , *GENE expression , *JANUS kinases , *GENES , *TUMORS , *MYELOID cells , *NEUROTRANSMITTER uptake inhibitors , *CARRIER proteins , *SYMPTOMS ,BONE marrow cancer - Abstract
Simple Summary: A group of blood diseases called myeloproliferative neoplasms (MPNs) cause a buildup of certain blood cell types in affected individuals. Each MPN category has a distinct clinical presentation and is associated with mutations in specific genes. However, these various categories all chronically switch on the same cellular pathway, involving signal transducer and activator of transcription (STAT) proteins. This perspective provides new insight for understanding and managing these important diseases. Myeloproliferative neoplasms (MPNs) are hematopoietic diseases characterized by the clonal expansion of single or multiple lineages of differentiated myeloid cells that accumulate in the blood and bone marrow. MPNs are grouped into distinct categories based on key clinical presentations and distinctive mutational hallmarks. These include chronic myeloid leukemia (CML), which is strongly associated with the signature BCR::ABL1 gene translocation, polycythemia vera (PV), essential thrombocythemia (ET), and primary (idiopathic) myelofibrosis (PMF), typically accompanied by molecular alterations in the JAK2, MPL, or CALR genes. There are also rarer forms such as chronic neutrophilic leukemia (CNL), which involves mutations in the CSF3R gene. However, rather than focusing on the differences between these alternate disease categories, this review aims to present a unifying molecular etiology in which these overlapping diseases are best understood as disruptions of normal hematopoietic signaling: specifically, the chronic activation of signaling pathways, particularly involving signal transducer and activator of transcription (STAT) transcription factors, most notably STAT5B, leading to the sustained stimulation of myelopoiesis, which underpins the various disease sequalae. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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