Microarray profiling and co-expression network analysis of the lncRNAs and mRNAs associated with acute leukemia in adults.

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis. The microarray revealed that 1011 lncRNAs and 2656 mRNAs differed in AML patients and 6069 lncRNAs and 5338 mRNAs differed in ALL patients from those in healthy controls. The GO terms and KEGG pathway annotation data revealed that the olfactory receptor activity, G-protein coupled receptor activity and olfactory transduction-related genes were significantly associated with AML and ALL. Co-expression network analysis indicated that 108 lncRNAs and 85 mRNAs were included in the co-expression network. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in AML and ALL using microarray technology and could provide basic information for new biomarkers or treatment targets to alleviate AML and ALL.

[1]  Mengchao Wu,et al.  An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma , 2016, Molecular Cancer Therapeutics.

[2]  F. Griggio,et al.  Abstract A27: European Network NGS-PTL preliminary data: Whole exome sequencing identifies mutations of ALDH2, RETSAT, HSPG2, CHPF and other metabolic genes as a novel functional category in acute myeloid leukemia , 2016 .

[3]  Alessandro Fatica,et al.  Long Non-Coding RNAs: New Players in Hematopoiesis and Leukemia , 2015, Front. Med..

[4]  Guido Marcucci,et al.  Expression and prognostic impact of lncRNAs in acute myeloid leukemia , 2014, Proceedings of the National Academy of Sciences.

[5]  Shaohua Chen,et al.  Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells , 2014, BMC Cancer.

[6]  A. Hoffman,et al.  A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies , 2014, Nucleic acids research.

[7]  Aristotelis Tsirigos,et al.  Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia , 2014, Cell.

[8]  C. Pui,et al.  VPREB1 deletions occur independent of lambda light chain rearrangement in childhood acute lymphoblastic leukemia , 2014, Leukemia.

[9]  A. Fatica,et al.  Long non-coding RNAs: new players in cell differentiation and development , 2013, Nature Reviews Genetics.

[10]  Jieqing Zhu,et al.  Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition , 2014, BMC Cancer.

[11]  I. Keklikoglou,et al.  Epigenetic Upregulation of lncRNAs at 13q14.3 in Leukemia Is Linked to the In Cis Downregulation of a Gene Cluster That Targets NF-kB , 2013, PLoS genetics.

[12]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[13]  W. Marsden I and J , 2012 .

[14]  Shuhan Sun,et al.  Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans , 2011, Hepatology.

[15]  Elisabeth F. Heuston,et al.  The Beginning of the Road for Non-Coding RNAs in Normal Hematopoiesis and Hematologic Malignancies , 2011, Front. Gene..

[16]  Anna L. Brown,et al.  Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia , 2011, Nature Genetics.

[17]  P. Fraser,et al.  No-Nonsense Functions for Long Noncoding RNAs , 2011, Cell.

[18]  Howard Y. Chang,et al.  Long noncoding RNA in genome regulation , 2010, RNA biology.

[19]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[20]  Leslie L Robison,et al.  Acute lymphoblastic leukaemia , 2018, Radiopaedia.org.

[21]  T. Golub,et al.  MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia , 2007, Proceedings of the National Academy of Sciences.

[22]  S. Fröhling,et al.  The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. , 2007, The Journal of clinical investigation.

[23]  M. Spitz,et al.  Myeloperoxidase G-463A polymorphism and lung cancer: A HuGE Genetic Susceptibility to Environmental Carcinogens pooled analysis , 2007, Genetics in Medicine.

[24]  C. Pui,et al.  New therapeutic strategies for the treatment of acute lymphoblastic leukaemia , 2007, Nature Reviews Drug Discovery.

[25]  Y. Hayashi,et al.  Common gene expression signatures in t(8;21)‐ and inv(16)‐acute myeloid leukaemia , 2006, British journal of haematology.

[26]  Yi Ning,et al.  Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. , 2006, Blood.

[27]  Y. Hayashi,et al.  KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. , 2006, Blood.

[28]  M. Relling,et al.  Bone marrow recurrence after initial intensive treatment for childhood acute lymphoblastic leukemia , 2005, Cancer.

[29]  Hung-Fat Tse,et al.  Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation , 2003, The Lancet.

[30]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[31]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.