Klin Padiatr 2018; 230(03): 165
DOI: 10.1055/s-0038-1644987
Top 1 Acute and chronic leukaemias
Georg Thieme Verlag KG Stuttgart · New York

Deciphering the genetically interactive network of the DLK1-DIO3 ncRNA locus in the hematopoietic system and pediatric acute megakaryoblastic leukemia

L Verboon
1   Martin-Luther-University Halle-Wittenberg
,
D Schneider
2   Hannover Medical School, Hannover
,
J Xu
3   UT Southwestern, Dallas, USA
,
D Heckl
2   Hannover Medical School, Hannover
,
JH Klusmann
1   Martin-Luther-University Halle-Wittenberg
› Author Affiliations
Further Information

Publication History

Publication Date:
08 May 2018 (online)

Also available at
 

Introduction:

Non-coding RNAs (ncRNAs) recently emerged as central regulators of chromatin and gene expression, posing a novel window for targeted therapies in pediatric acute megakaryoblastic leukemia (AMKL).

Results:

We established a comprehensive lncRNA expression atlas for the hematopoietic system including 46 pediatric acute myeloid leukemia patient samples, and discovered a cluster within the DLK1-DIO3 locus on chromosome 14 that was highly expressed in hematopoietic stem cells (HSCs), megakaryocytes and AMKL. ChIP-Seq performed for human megakaryocytes, monocytes and CD34+ HSPCs showed cell type specific histone marks in the locus, especially for MEG3. Deletion of MEG3 and MEG8 in HEL and K562 cells, using the CRISPR-Cas9 system, resulted in an increase in cell size and subsequent cell death.

Conclusion:

Our study provides possible targets in the treatment of AMKL within the DLK1-DIO3 locus.