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      Aberrant LncRNA Expression in Leukemia

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          Abstract

          Leukemia is a common malignant cancer of the hematopoietic system, whose pathogenesis has not been fully elucidated. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding function. Recent studies report their role in cellular processes such as the regulation of gene expression, as well as in the carcinogenesis, occurrence, development, and prognosis of various tumors. Evidence indicating relationships between a variety of lncRNAs and leukemia pathophysiology has increased dramatically in the previous decade, with specific lncRNAs expected to serve as diagnostic biomarkers, novel therapeutic targets, and predictors of clinical outcomes. Furthermore, these lncRNAs might offer insight into disease pathogenesis and novel treatment options. This review summarizes progress in studies on the role(s) of lncRNAs in leukemia.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Miao-Chih Tsai, Ohad Manor, Yue Wan … (2010)
          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene.

            Y Kotake, T. Nakagawa, K Kitagawa … (2011)
            A 42 kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors. The expression of the INK4A-ARF-INK4B gene cluster is silenced by polycomb during normal cell growth and is activated by oncogenic insults and during aging. How the polycomb is recruited to repress this gene cluster is unclear. Here, we show that expression of oncogenic Ras, which stimulates the expression of p15(INK4B) and p16(INK4A), but not p14(ARF), inhibits the expression of ANRIL (antisense non-coding RNA in the INK4 locus), a 3.8 kb-long non-coding RNA expressed in the opposite direction from INK4A-ARF-INK4B. We show that the p15(INK4B) locus is bound by SUZ12, a component of polycomb repression complex 2 (PRC2), and is H3K27-trimethylated. Notably, depletion of ANRIL disrupts the SUZ12 binding to the p15(INK4B) locus, increases the expression of p15(INK4B), but not p16(INK4A) or p14(ARF), and inhibits cellular proliferation. Finally, RNA immunoprecipitation demonstrates that ANRIL binds to SUZ12 in vivo. Collectively, these results suggest a model in which ANRIL binds to and recruits PRC2 to repress the expression of p15(INK4B) locus.
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              Acute lymphoblastic leukemia: a comprehensive review and 2017 update

              T Terwilliger, M Abdul-Hay (2017)
              Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (iso-abbrev): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2020
                Publication date (Electronic): 27 April 2020
                Volume: 11
                Issue: 14
                Pages: 4284-4296
                Affiliations
                Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
                Author notes
                ✉ Corresponding author: Yongqian Jia, Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. E-mail: jia_yq@ 123456scu.edu.cn

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: jcav11p4284
                DOI: 10.7150/jca.42093
                PMC ID: 7196264
                PubMed ID: 32368311
                SO-VID: c7583a0a-2cec-47dd-91bf-80988ca0f382
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 14 November 2019
                Date accepted : 31 March 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: long non-coding rnas (lncrnas),leukemia,transcription regulation,expression profiling,therapeutic targets
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: long non-coding rnas (lncrnas), leukemia, transcription regulation, expression profiling, therapeutic targets

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