8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia

Abstract

The pathogenetic roles of 8q24 amplified segments in leukemic cells with double minute chromosomes remain to be verified. Through comprehensive molecular analyses of 8q24 amplicons in leukemic cells from an acute myelogenous leukemia (AML) patient and AML-derived cell line HL60 cells, we identified two novel fusion genes between NSMCE2 and long noncoding RNAs (lncRNAs), namely, PVT1-NSMCE2 and BF104016-NSMCE2. Our study suggests that 8q24 amplicons are associated with the emergence of aberrant chimeric genes between NSMCE2 and oncogenic lncRNAs, and also implicate that the chimeric genes involving lncRNAs potentially possess as-yet-unknown oncogenic functional roles.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0068-2) contains supplementary material, which is available to authorized users.

<b><i>MYC</i></b> Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2)

“…In case 5, high-resolution oligonucleotide array detected MYC amplification. In addition to marker chromosomes, the presence of dmin was demonstrated by metaphase FISH [Chinen et al, 2014]. In contrast, case 6 showed MYC amplification in marker chromosomes and EZH2 microdeletion [Xiang et al, 2015].…”

Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

“…Although not expressed in normal myelopoiesis, in an AML patient sample and an AML-derived HL-60 cell line, contain a rearrangement of the lncRNA gene Non-Structural Maintenance Of Chromosomes Element 2 Homolog (NSMCE2) that gives rise to two novel chimeric genes, PVT1-NSMCE2 and CCDC26-NSMCE2 [92]. Beyond hypothesizing an oncogenic role of plasmacytoma variant translocation 1 (PVT1) and coiled-coil domain-containing protein 26 (CCDC26) [93] a role in leukemogenesis has not been determined, however the concept of fusion transcripts of lncRNA and coding genes adds yet another layer of complexity to the lncRNA world.…”

Long noncoding RNAs: pivotal regulators in acute myeloid leukemia

“…In an AML patient sample and an AML-derived HL-60 cell line, it is verified that NSMCE2 rearrangement gives rise to two novel chimeric genes, PVT1-NSMCE2 and CCDC26-NSMCE2 [12]. Although their identities have been revealed, their involvement in leukemogenesis is elusive to date.…”

“…Based on the genomic locations where lncRNAs are transcribed, they can be classified into the following groups: (1) sense, which overlap with at least part of another gene in the same strand; (2) antisense, which overlap with at least part of another gene on the opposite strand; (3) intronic, which originate from the intron of another gene; (4) intergenic, which does not overlap with any gene. In addition to the above four classes, it is possible to characterize an additional fifth category: (5) chimeric, which are the fusion products due to chromosomal rearrangements, based on a study showing the existence of fusion transcripts between protein-coding genes and lncRNAs in AML [12]. Since only two known protein-lncRNA fusions have been identified in AML and their function has not been elucidated [12], the further investigation would be required.…”

“…In addition to the above four classes, it is possible to characterize an additional fifth category: (5) chimeric, which are the fusion products due to chromosomal rearrangements, based on a study showing the existence of fusion transcripts between protein-coding genes and lncRNAs in AML [12]. Since only two known protein-lncRNA fusions have been identified in AML and their function has not been elucidated [12], the further investigation would be required. In this review, we summarize the recent progress in the knowledge of lncRNAs in AML, including their biological functions, the mechanisms behind their actions, the upstream regulation and the prognostic values in the clinic.…”