Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiR-3151 interplays with its host gene BAALC and independently impacts on outcome of patients with cytogenetically normal acute myeloid leukemia - expression microarray data

ABSTRACT: Recently, deep sequencing of melanoma and pediatric acute lymphoblastic leukemia samples identified a new microRNA - miR-3151 - embedded in intron 1 of the BAALC gene. MiR genes are located throughout the genome, but about one-third of mammalian miRs reside within introns of host genes. Some of these intronic miRs have been found to act in functional synergism with their host genes. These findings led us to hypothesize that miR-3151 could be overexpressed in patients with elevated BAALC levels and thus might contribute to the adverse prognostic impact of its host gene, either acting in concert with BAALC or perhaps even being the element predominantly responsible for the adverse outcome observed in BAALC overexpressing AML patients.Thus, we have measured miR-3151 and BAALC expression in a cohort of molecularly well characterized de novo CN-AML patients to assess the impact of miR-3151 expression alone and in combination with its host BAALC on outcome. microRNA expression profiles associated with miR-3151 expression in older patients with cytogenetically normal acute myeloid leukemia were derived using microarrays. The corresponding microRNA expression data can be found under accession number E-MTAB-1074.

ORGANISM(S): Homo sapiens

SUBMITTER: Guido Marcucci

PROVIDER: E-MTAB-1075 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Somatic and germline mutations in GATA2 were recently identified in patients diagnosed with monoMAC, the hallmarks of which include monocytopenia, B-cell and NK-cell lymphopenia, susceptibility to opportunistic infections (e.g. MAC), and a strong propensity to develop hypocellular MDS/AML or CMML. GATA2 mutations are thought to result in loss of function or haploinsufficiency, but the precise mechanism for the development of cytopenias, immunodeficiency, and susceptibility to MDS remains to be elucidated. MicroRNA (miR) represents a unique mechanism of post-transcriptional gene regulation. In this study we generated microRNA profiles of patient derived monoMAC cell lines followed by functional studies to identify aberrant miRs and their targets, which could potentially cooperate with GATA2 deficiency in generating cytopenias and hematologic disease. In our study, eight miRs were significantly differentially expressed (≥ 2-fold; p ≤ 0.05) as determined by microRNA microarray profiles; miR-9, miR-181a-2-3p, miR-181c, miR-181c-3p, miR-486-3p, and miR-582-5p showed increased expression in monoMAC cell lines compared to controls, while miR-223 and miR-424-3p showed significantly decreased expression. Among the differentially expressed miRs that were validated by quantitative RT-PCR was miR-181c, which demonstrated a 2.2 fold increase in expression in monoMAC cell lines (p = 0.013). Among the target transcripts potentially regulated by miR-181c, MCL1 expression was significantly decreased (2 fold; p = 0.018) in monoMAC cell lines in comparison to control cell lines. Transient transfection of miR-181c in Ly8 cells resulted in 40% decrease of MCL1 mRNA level, suggesting that miR-181c negatively regulates MCL1 in MonoMAC. These findings indicate that monoMAC/GATA2 deficiency is associated with significantly decreased expression of MCL1 possibly through negative regulation involving miR-181c. Deletion of Mcl1 is known to cause apoptosis, loss of HSCs, and cytopenias in murine studies. Thus, down-regulation of MCL1 seen in monoMAC/GATA2 deficiency may similarly favor unregulated apoptosis and the depletion of hematopoietic progenitors resulting in cytopenias, immunodeficiency, and risk of MDS/AML.

Dataset Information

MiR-3151 interplays with its host gene BAALC and independently impacts on outcome of patients with cytogenetically normal acute myeloid leukemia - expression microarray data

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets