MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia

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BlankBlood First Edition Paper, prepublished online February 4, 2011; DOI

10.1182/blood-2010-05-285064.

MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic

leukemia

Karin Vargova1, Nikola Curik1, Pavel Burda1, Petra Basova1, Vojtech Kulvait1,

Vit Pospisil1, Filipp Savvulidi1, Juraj Kokavec1, Emanuel Necas1, Adela

Berkova2, Petra Obrtlikova2, f Karban1, Marek Mraz3, Sarka Pospisilova3,

Jiri Mayer3, Marek Trneny2, Jiri Zavadil4 and Tomas Stopka1,*

1 First Faculty of Medicine and Center of Experimental Hematology,

University in Prague, Prague, Czech Republic; 2 First Medical Department -

Hematology, General Faculty Hospital, Prague, Czech Republic; 3 Department of

Internal Medicine - Hematooncology, University Hospital Brno and Medical

Faculty, Masaryk University, Brno, Czech Republic; 4 Pathology, NYU Cancer

Institute and Center for Health Informatics and Bioinformatics, New York

University Langone Medical Center, New York, United States

* Corresponding author; email: tstopka@...

Abstract

Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in

chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that

MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset

of B-CLL patients. MYB physically associates with the promoter of MIR155 host

gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates

its transcription. This coincides with the hypermethylated histone H3K4 residue

and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide

evidence of oncogenic activities of MYB in B-CLL that include its stimulatory

role in MIR155HG transcription.