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| Status |
Public on Dec 07, 2019 |
| Title |
Expression data of HEL cells with or without LY2784544 and GRN163L |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The mutant JAK2v617F is a driver of myeloproliferative neoplasms(MPNs). Consequently, several JAK2 inhibitors are currently being studied in clinical trials. The most investigated JAK2 inhibitor, Ruxolitinib, provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease and represents a milestone in the treatment of myelofibrosis. However, JAK2 inhibitors are non-curative and murine experiments have shown that JAK2 inhibitors don?t eradicate MPN stem cells. In the present study, we determined the effect of the specific JAK2V617F inhibitor LY2784544 on leukemic stem (CD34+) cells (LSCs) using the JAK2V617F-bearing erythroleukemia cell line HEL. The LY2784544 treatment caused a transient proliferation inhibition and apoptosis of HEL cells, but a recovery occurred within a week. Thereafter, the continuous exposure of HEL cells to LY2784544 induced the accumulation of CD34+ LSCs, and the CD34+ cell fraction increased from 8% to over 90% by week 9, which was accompanied by substantially increased clonogenic potentials. A whole-transcript expression analysis revealed a significantly enhanced expression of the stem cell factor KLF4 in LY2784544 treated HEL cells. Inhibiting KLF4 expression attenuated LY2784544-mediated accumulation of CD34+ LSCs. Moreover, we further identified that the telomerase inhibitor GRN163L abolished the LY2784544-mediated CD34+ cell enrichment. Our findings collectively suggest that JAK2 inhibitors may cause enrichment of LSCs and are therefore unlikely to cure MPN as a monotherapy. Moreover, simultaneously targeting JAk2V617F and KLF4 or telomerase may be a novel strategy for MPN treatment.
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| Overall design |
We detected the expression file of HEL cell line after treated with JAK2 inhibitor LY2784544, telomerase inhibitor GRN163L, combination of LY2784544 and GRN163L, experiment were conducted twice seperately
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| Contributor(s) |
Dahlström J, Xu D, Björkholm M, Xia C, Yuan X, Xing X |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 06, 2019 |
| Last update date |
Dec 09, 2019 |
| Contact name |
Jenny Dahlström |
| E-mail(s) |
jenny.e.dahlstrom@gmail.com
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| Organization name |
Karolinska Institutet
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| Department |
Medicine
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| Lab |
Hematology
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| Street address |
Solnavägen 1
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| City |
Stockholm |
| ZIP/Postal code |
17177 |
| Country |
Sweden |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA594024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141602_RAW.tar |
36.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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