The role of HMGA2 in myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the activation of the JAK-STAT pathway due to driver mutations, including JAK2V617F, but some additional abnormalities may be necessary to maintain an MPN clone and develop a more advanced disease. The HMGA2 proto-oncogene, which regulates the...

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Bibliographic Details
Published inRinshō ketsueki Vol. 59; no. 10; p. 2067
Main Author Ikeda, Kazuhiko
Format Journal Article
LanguageJapanese
Published Japan 2018
Subjects
Animals
Enhancer of Zeste Homolog 2 Protein - genetics
HMGA2 Protein - genetics
Humans
Janus Kinase 2 - genetics
Mice
MicroRNAs - genetics
Mutation
Myeloproliferative Disorders - genetics
Neoplasms - genetics
Primary Myelofibrosis - genetics
HMGA2
let-7
Myeloproliferative neoplasms
EZH2
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Summary:Myeloproliferative neoplasms (MPNs) are characterized by the activation of the JAK-STAT pathway due to driver mutations, including JAK2V617F, but some additional abnormalities may be necessary to maintain an MPN clone and develop a more advanced disease. The HMGA2 proto-oncogene, which regulates the expression of various genes, is often overexpressed due to downregulation of let-7 microRNAs or EZH2 mutations in advanced MPNs such as myelofibrosis. In mice with JAK2V617F, Ezh2 deletion deregulates Hmga2, which plays a crucial role in MPN progression. Correspondingly, Hmga2 overexpression causes massive splenomegaly and severe anemia in mice carrying JAK2V617F, mimicking severe MPN. Herein, we discuss the mechanisms of HMGA2 deregulation and its possible use as a therapeutic target.
ISSN:0485-1439
DOI:10.11406/rinketsu.59.2067