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Abstract
BackgroundAcute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.FindingsIn this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited.ConclusionOur findings reveal that the lncRNA PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0223-4) contains supplementary material, which is available to authorized users.
Highlights
Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes
Our findings reveal that the long non-coding RNA (lncRNA) PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management
PVT1 is upregulated in APL To investigate whether PVT1 is involved in the development of APL, we initially compared the PVT1 expression in primary APL patient samples with that in healthy donors
Summary
Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have been used in APL therapy to induce the degradation of the key leukemogenic protein PML-RARα [3, 4]. Transcription factors such as PU. are involved in the pathogenesis of APL [3, 5, 6]. LncRNAs have been demonstrated to regulate gene expression through epigenetic, transcriptional, and posttranscriptional regulation, and they are involved in X chromosome silencing, genomic imprinting, chromatin modifications, and other important regulatory processes [14, 16,17,18,19,20,21].
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