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| Status |
Public on Dec 09, 2022 |
| Title |
The miR-497~195 cluster suppresses cell cycle regulators and in vivo leukemia growth in B-cell precursor Acute Lymphoblastic Leukemia [expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Despite considerable improvements in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), relapse is still associated with poor prognosis. We previously found that the risk for early relapse can be predicted by the rapid engraftment of patient-derived blasts transplanted into NOD/SCID mice. In search for the cellular and molecular profile associated with this phenotype, we investigated the expression of microRNAs (miRNAs) in different engraftment phenotypes and patient outcomes. We found miR-497~195 high expression in patient-derived xenograft samples with slow engraftment, derived from patients with favorable outcome. In contrast, epigenetic repression and low expression of these miRNAs was observed in rapidly engrafting samples, which were associated with early relapse. Overexpression of miR-497~195 in patient-derived cells suppressed in vivo engraftment of leukemia cells and considerably prolonged recipient survival by inhibition of regulators of cell cycle progression. As key factors for the entry in S phase were downregulated upon miR-497~195 overexpression, we identified CDK4/CCND3 mediated control of G1/S transition as a principal mechanism for miR-497~195 mediated suppression of leukemia progression in BCP-ALL. Thus, the association of the miR-497~195 cluster expression with outcome in BCP-ALL, and the importance of these miRNAs in counteracting the development of ALL in vivo indicate the relevance of the involved pathways as potential targets for therapeutic intervention.
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| Overall design |
BCP-ALL cell transduced with empty vector (N=5) and with miR-497~195 (N=4)
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| Contributor(s) |
Boldrin E, Gaffo E, Boer J, Demir S, Zinngrebe J, Seyfried F, Claus R, Plass C, Boer MD, Debatin K, Kronnie G, Bortoluzzi S, Meyer LH |
| Citation(s) |
34098582 |
| |
| Submission date |
Dec 10, 2019 |
| Last update date |
Nov 05, 2024 |
| Contact name |
Stefania Bortoluzzi |
| E-mail(s) |
stefania.bortoluzzi@unipd.it
|
| Phone |
++30 049 827 6502
|
| Organization name |
University of Padova
|
| Department |
Department of Molecular Medicine
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| Lab |
Computational Genomics
|
| Street address |
via G. Colombo 3
|
| City |
Padova |
| ZIP/Postal code |
35131 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE141780 |
The miR-497~195 cluster suppresses cell cycle regulators and in vivo leukemia growth in B-cell precursor Acute Lymphoblastic Leukemia |
|
| Relations |
| BioProject |
PRJNA594702 |
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