Identification of AIM2 as a downstream target of JAK2V617F

Experimental Hematology & Oncology
Ei Leen LiewN Komatsu

Abstract

The gain-of-function mutation JAK2V617F is frequently found in Philadelphia-chromosome-negative myeloproliferative neoplasm (MPN) patients. However, the tumorigenic properties of JAK2V617F have mostly been characterized in in vivo and in vitro murine models due to the lack of appropriate human cell lines. Using the multipotent hematologic cell line UT-7/GM, we established D9, a novel human cell line that expresses JAK2V617F upon tetracycline addition. We assessed cellular differentiation in UT-7/GM cells when JAK2V617F was induced, and we used microarrays to analyze changes in mRNA expression caused by JAK2V617F. Using the human D9 cell line, we demonstrated that the induction of JAK2V617F leads to cytokine-independent cell growth with increased STAT activation and erythroid differentiation, mimicking the characteristics observed in polycythemia vera, making it a suitable in vitro model for studying this disorder. Interestingly, JAK2V617F-dependent erythroid cell differentiation was blocked when GM-CSF was added to the culture, suggesting that the GM-CSF pathway antagonizes JAK2V617F-induced erythroid cell differentiation. Our microarray analysis identified several genes involved in inflammasome activation, such as AIM2, IL1B, ...Continue Reading

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Citations

Jul 28, 2020·Journal of Clinical Medicine·Lucia LonghitanoGiuseppe Alberto Palumbo
Jan 14, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lijing YangJunping Wang
Jan 13, 2021·International Journal of Molecular Sciences·Valeria Di BattistaAlessandro Lucchesi
Apr 29, 2021·Journal of Inflammation Research·Ting-Ting ChenWu-Yi Sun

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
PCR
Protein Assay
transfection

Software Mentioned

ssGSEA
SAM
ROC

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