Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes.

Maxime Caron,Guillaume Bourque,Pascal St-Onge,Simon Drouin,Stephan Busche,Daniel Sinnett,Thomas Sontag,Chantal Richer,Tomi Pastinen,Obul Reddy Bandapalli

doi:10.1371/journal.pone.0207250

Abstract

Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (~50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs are still unknown, our results suggest they could play a role in cALL etiology or progression.

Highlights

Childhood acute lymphoblastic leukemia represents approximately 25% of all pediatric cancer cases
We sequenced the whole transcriptome of 64 Childhood acute lymphoblastic leukemia (cALL) patients (57 pre-B and 7 pre-T) and 4 matched normal cell populations derived from human cord blood (3 CD10+CD19+ pre-B and 1 CD3+ pre-T) (S1 Table; [6])
When compared to available public datasets [8, 9], we found that 59% (574 / 971) of vlincRNAs were unique and specific to our cALL samples (< 25% reciprocal strand specific overlap) while the remaining 41% overlapped with those found in at least one existing dataset (Fig 1C and 1D)

Summary

Introduction

Childhood acute lymphoblastic leukemia (cALL) represents approximately 25% of all pediatric cancer cases. Despite remarkable improvements in survival, with 5 year event-free survival rates of approximately 80%, non-responding or relapsing patients still represent one of the most frequent cause of disease-related death in children [1]. Childhood ALL is a complex disease comprising multiple molecular subtypes with distinctive somatic genetic alterations such as aneuploidy, chromosomal rearrangements, and point mutations [1]. High hyperdiploid cases (HHD) and those harboring the t(12;21) [ETV6/RUNX1] rearrangement, together representing about half of pre-B cALL cases. Both subtypes are associated with a good prognosis [1, 2]. ~75% of cALL cases can be currently sub-classified clinically using standard

Methods

Results

Conclusion