The Novel LncRNA BlackMamba Controls the Neoplastic Phenotype of ALK Anaplastic Large Cell Lymphoma by Regulating the DNA Helicase HELLS

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2020 Mar 4

PMID 32123306

Citations 11

Authors

Valentina Fragliasso

Akanksha Verma

Gloria Manzotti

Annalisa Tameni

Rohan Bareja

Tayla B Heavican

Javeed Iqbal

Rui Wang

Danilo Fiore

Valentina Mularoni

Wing C Chan

Priscillia Lhoumaud

Jane Skok

Eleonora Zanetti

Francesco Merli

Alessia Ciarrocchi

Oliver Elemento

Giorgio Inghirami

Affiliations

Soon will be listed here.

Abstract

The molecular mechanisms leading to the transformation of anaplastic lymphoma kinase negative (ALK) anaplastic large cell lymphoma (ALCL) have been only in part elucidated. To identify new culprits which promote and drive ALCL, we performed a total transcriptome sequencing and discovered 1208 previously unknown intergenic long noncoding RNAs (lncRNAs), including 18 lncRNAs preferentially expressed in ALCL. We selected an unknown lncRNA, BlackMamba, with an ALK ALCL preferential expression, for molecular and functional studies. BlackMamba is a chromatin-associated lncRNA regulated by STAT3 via a canonical transcriptional signaling pathway. Knockdown experiments demonstrated that BlackMamba contributes to the pathogenesis of ALCL regulating cell growth and cell morphology. Mechanistically, BlackMamba interacts with the DNA helicase HELLS controlling its recruitment to the promoter regions of cell-architecture-related genes, fostering their expression. Collectively, these findings provide evidence of a previously unknown tumorigenic role of STAT3 via a lncRNA-DNA helicase axis and reveal an undiscovered role for lncRNA in the maintenance of the neoplastic phenotype of ALKALCL.

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