Oncotarget

Research Papers:

Generation and characteristics of a novel “double-hit” high grade B-cell lymphoma cell line DH-My6 with MYC/IGH and BCL6/IGH gene arrangements and potential molecular targeted therapies

Hiroaki Kikuchi, Tomonori Higuchi, Yumiko Hashida, Ayuko Taniguchi, Mikio Kamioka, Takahiro Taguchi, Akihito Yokoyama, Ichiro Murakami, Mikiya Fujieda and Masanori Daibata _

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Oncotarget. 2018; 9:33482-33499. https://doi.org/10.18632/oncotarget.26060

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Abstract

Hiroaki Kikuchi1,2, Tomonori Higuchi1, Yumiko Hashida1, Ayuko Taniguchi3, Mikio Kamioka4, Takahiro Taguchi5, Akihito Yokoyama3, Ichiro Murakami6, Mikiya Fujieda2 and Masanori Daibata1

1Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

2Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

3Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

4Department of Laboratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

5Department of Molecular and Cellular Biology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

6Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan

Correspondence to:

Masanori Daibata, email: daibatam@kochi-u.ac.jp

Keywords: double hit lymphoma; MYC; BCL6; PLK1; HDAC

Received: June 21, 2018     Accepted: August 10, 2018     Published: September 11, 2018

ABSTRACT

“Double-hit” lymphoma (DHL) is a high-grade B-cell lymphoma that harbors concurrent MYC and BCL2 or BCL6 rearrangements. Because cases of MYC/BCL6 DHL are uncommon, most reported conclusions have been based on cases of MYC/BCL2 DHL. Lack of experimental MYC/BCL6 DHL models continues to hinder the pathophysiologic and therapeutic investigations of this disorder. We herein describe a novel MYC/BCL6 DHL cell line, designated DH-My6, carrying both the MYCIGH and BCL6IGH fusion genes. Interruptions of MYC and BCL6 expressions using short interfering RNAs and chemical inhibitors led to significant attenuation of DH-My6 cell growth. Greater antitumor effects were found when the cells were treated with a combination of MYC and BCL6 inhibitors. Moreover, the PLK1 inhibitor volasertib and the HDAC inhibitor vorinostat synergized strongly when combined with the bromodomain inhibitor JQ1. DH-My6 is a new well-validated MYC/BCL6 DHL cell line that will provide a useful model for studies of the pathogenesis and therapeutics for the less common DHL tumor type. The rationale for approaches targeting both MYC and BCL6, and in combination with PLK1 or HDAC inhibitors for superior suppression of the aggressive MYC/BCL6 DHL warrants further in vivo testing in a preclinical model.


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