Klin Padiatr 2017; 229(03): 182-195
DOI: 10.1055/s-0037-1602219
Top 5 Cell biology and mechanisms of disease
Georg Thieme Verlag KG Stuttgart · New York

Expression and impact of miR-497˜195 in pediatric ALL

E Boldrin
1   Dept. of Pediatrics and Adolescent Medicine, Ulm University, Ulm, Germany
,
E Gaffo
2   Dept. of Molecular Medicine, Padua University, Padua, Italy
,
G te Kronnie
3   Dept. of Woman and Child Health, Padua University, Padua, Italy
,
S Bortoluzzi
2   Dept. of Molecular Medicine, Padua University, Padua, Italy
,
KM Debatin
1   Dept. of Pediatrics and Adolescent Medicine, Ulm University, Ulm, Germany
,
LH Meyer
1   Dept. of Pediatrics and Adolescent Medicine, Ulm University, Ulm, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
30 May 2017 (online)

Also available at
 

Introduction:

Fast engraftment of Acute Lymphoblastic Leukemia (ALL) samples in NOD/SCID mice (short Time To Leukemia: TTLshort) is associated with patient treatment outcome and early relapse.

Methods:

Small RNA sequencing was performed in B-cell precursor (BCP)-ALL patient-derived xenograft samples. The function of miRNAs was investigated by stable overexpression in BCP-ALL cell lines and transplantation in the NOD/SCID mouse model.

Results:

We found 18 miRNAs differentially expressed in samples with TTLlong vs. TTLshort phenotype. The tumor suppressor miR-497˜195 cluster was identified to be downregulated in TTLshort group by hypermethylation of the promoter. Transplantation of BCP-ALL cells with miR-497˜195 overexpression resulted in decreased engraftment and leukemia load as compared to control cells.

Conclusions:

Our findings show that low miR-497˜195 expression is associated with rapid NOD/SCID engraftment/patient relapse in BCP-ALL. Moreover, forced miR-497˜195 overexpression decelerates engraftment and leukemia occurrence in vivo.