Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

MicroRNAs and noncoding RNAs in hematological malignancies: molecular, clinical and therapeutic implications

Leukemia volume 22, pages 1095–1105 (2008)Cite this article

Abstract

MicroRNAs (miRNAs) are a family of 19–24 nucleotide noncoding RNAs (ncRNAs) with posttranscriptional regulatory functions. Increasing evidences from the literature show that miRNAs play a pivotal role in human tumorigenesis. Many studies have addressed the role of miRNAs in normal hematopoiesis, giving an interpretative key to the aberrancies of expression observed in human hematological malignancies. Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype. Here we review the main studies investigating the role of miRNAs and UCRs in both normal hemopoiesis and hematological malignancies, and identify the molecular, clinical and therapeutic implications of these recent findings.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T . Identification of novel genes coding for small expressed RNAs. Science 2001; 294: 853–858.

    CAS  PubMed  Google Scholar 

  2. Lau NC, Lim LP, Weinstein EG, Bartel DP . An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001; 294: 858–862.

    CAS  PubMed  Google Scholar 

  3. Lee RC, Ambros V . An extensive class of small RNAs in Caenorhabditis elegans. Science 2001; 294: 862–864.

    CAS  PubMed  Google Scholar 

  4. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004; 23: 4051–4060.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Cai X, Hagedorn CH, Cullen BR . Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004; 10: 1957–1966.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ambros V . The functions of animal microRNAs. Nature 2004; 431: 350–355.

    CAS  PubMed  Google Scholar 

  7. Bohnsack MT, Czaplinski K, Gorlich D . Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004; 10: 185–191.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U . Nuclear export of microRNA precursors. Science 2004; 303: 95–98.

    CAS  PubMed  Google Scholar 

  9. Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.

    CAS  PubMed  Google Scholar 

  10. Saito K, Ishizuka A, Siomi H, Siomi MC . Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol 2005; 3: e235.

    PubMed  PubMed Central  Google Scholar 

  11. Gregory RI, Chendrimada TP, Shiekhattar R . MicroRNA biogenesis: isolation and characterization of the microprocessor complex. Methods Mol Biol 2006; 342: 33–47.

    CAS  PubMed  Google Scholar 

  12. He L, Hannon GJ . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5: 522–531.

    CAS  PubMed  Google Scholar 

  13. Pasquinelli AE, Hunter S, Bracht J . MicroRNAs: a developing story. Curr Opin Genet Dev 2005; 15: 200–205.

    CAS  PubMed  Google Scholar 

  14. Harfe BD . MicroRNAs in vertebrate development. Curr Opin Genet Dev 2005; 15: 410–415.

    CAS  PubMed  Google Scholar 

  15. Carleton M, Cleary MA, Linsley PS . MicroRNAs and cell cycle regulation. Cell Cycle 2007; 6: 2127–2132.

    CAS  PubMed  Google Scholar 

  16. Williams AE, Perry MM, Moschos SA, Lindsay MA . MicroRNA expression in the aging mouse lung. BMC Genomics 2007; 8: 172.

    PubMed  PubMed Central  Google Scholar 

  17. Wang E . MicroRNA, the putative molecular control for mid-life decline. Ageing Res Rev 2007; 6: 1–11.

    PubMed  Google Scholar 

  18. Boehm M, Slack FJ . MicroRNA control of lifespan and metabolism. Cell Cycle 2006; 5: 837–840.

    CAS  PubMed  Google Scholar 

  19. Sevignani C, Calin GA, Siracusa LD, Croce CM . Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 2006; 17: 189–202.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M et al. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 2004; 101: 9740–9744.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 2007; 12: 215–229.

    CAS  PubMed  Google Scholar 

  22. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS et al. Ultraconserved elements in the human genome. Science 2004; 304: 1321–1325.

    CAS  PubMed  Google Scholar 

  23. Bejerano G, Haussler D, Blanchette M . Into the heart of darkness: large-scale clustering of human non-coding DNA. Bioinformatics 2004; 20 (Suppl 1): I40–I48.

    CAS  PubMed  Google Scholar 

  24. Georgantas III RW, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 2007; 104: 2750–2755.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 2005; 123: 819–831.

    CAS  PubMed  Google Scholar 

  26. Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F et al. MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol 2007; 9: 775–787.

    CAS  PubMed  Google Scholar 

  27. Bruchova H, Yoon D, Agarwal AM, Mendell J, Prchal JT . Regulated expression of microRNAs in normal and polycythemia vera erythropoiesis. Exp Hematol 2007; 35: 1657–1667.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 2005; 102: 18081–18086.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R et al. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sc USA 2006; 103: 5078–5083.

    CAS  Google Scholar 

  30. Monticelli S, Ansel KM, Xiao C, Socci ND, Krichevsky AM, Thai TH et al. MicroRNA profiling of the murine hematopoietic system. Genome Biol 2005; 6: R71.

    PubMed  PubMed Central  Google Scholar 

  31. Zhou B, Wang S, Mayr C, Bartel DP, Lodish HF . MiR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci USA 2007; 104: 7080–7085.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J et al. MiR-150 Controls B Cell Differentiation by Targeting the Transcription Factor c-Myb. Cell 2007; 131: 146–159.

    CAS  PubMed  Google Scholar 

  33. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci USA 2006; 103: 7024–7029.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y et al. Regulation of the germinal center response by microRNA-155. Science 2007; 316: 604–608.

    CAS  PubMed  Google Scholar 

  35. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007; 316: 608–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen CZ, Li L, Lodish HF, Bartel DP . MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83–86.

    CAS  PubMed  Google Scholar 

  37. Neilson JR, Zheng GX, Burge CB, Sharp PA . Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 2007; 21: 578–589.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Nakayama T, Kasprowicz DJ, Yamashita M, Schubert LA, Gillard G, Kimura M et al. The generation of mature, single-positive thymocytes in vivo is dysregulated by CD69 blockade or overexpression. J Immunol 2002; 168: 87–94.

    CAS  PubMed  Google Scholar 

  39. Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G et al. MiR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007; 129: 147–161.

    CAS  PubMed  Google Scholar 

  40. Ramkissoon SH, Mainwaring LA, Ogasawara Y, Keyvanfar K, McCoy Jr JP, Sloand EM, Kajigaya S, Young NS . Hematopoietic-specific microRNA expression in human cells. Leuk Res 2006; 30: 643–647.

    CAS  PubMed  Google Scholar 

  41. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999–3004.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Calin GA, Croce CM . Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest 2007; 117: 2059–2066.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mott JL, Kobayashi S, Bronk SF, Gores GJ . mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 2007; 26: 6133–6140.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 2007; 104: 15805–15810.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V et al. TCL1 expression in CLL is regulated by miR-29 and miR-181. Cancer Res 2006; 66: 11590–11593.

    Article  CAS  PubMed  Google Scholar 

  46. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T . Identification of tissue-specific microRNAs from mouse. Curr Biol 2002; 12: 735–739.

    CAS  PubMed  Google Scholar 

  47. Sanchez-Izquierdo D, Buchonnet G, Siebert R, Gascoyne RD, Climent J, Karran L et al. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. Blood 2003; 101: 4539–4546.

    CAS  PubMed  Google Scholar 

  48. Sonoki T, Iwana E, Mitsuya H, Asou N . Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia. Leukemia 2005; 19: 2009–2010.

    CAS  PubMed  Google Scholar 

  49. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A et al. MicroRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sc USA 2006; 103: 9136–9141.

    CAS  Google Scholar 

  50. Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 2007; 67: 2456–2468.

    CAS  PubMed  Google Scholar 

  51. Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA 2007; 104: 8017–8022.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 2005; 102: 3627–3632.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A . High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer 2004; 39: 167–169.

    CAS  PubMed  Google Scholar 

  54. Kluiver J, Haralambieva E, de Jong D, Blokzijl T, Jacobs S, Kroesen BJ et al. Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma. Genes Chromosomes Cancer 2006; 45: 147–153.

    CAS  PubMed  Google Scholar 

  55. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 2005; 207: 243–249.

    CAS  PubMed  Google Scholar 

  56. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B et al. Modulation of miR-155 and miR-125b Levels following lipopolysaccharide/TNF-{alpha} stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 2007; 179: 5082–5089.

    CAS  PubMed  Google Scholar 

  57. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 2004; 101: 11755–11760.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA 2007; 104: 16170–16175.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Skalsky RL, Samols MA, Plaisance KB, Boss IW, Riva A, Lopez MC et al. Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. J Virol 2007; 81: 12836–12845.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Martin MM, Lee EJ, Buckenberger JA, Schmittgen TD, Elton TS . MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J Biol Chem 2006; 281: 18277–18284.

    CAS  PubMed  Google Scholar 

  61. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S et al. A microRNA polycistron as a potential human oncogene. Nature 2005; 435: 828–833.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT . c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839–843.

    CAS  PubMed  Google Scholar 

  63. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65: 9628–9632.

    CAS  PubMed  Google Scholar 

  64. Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, Paterson JC et al. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 2007; 121: 1156–1161.

    CAS  PubMed  Google Scholar 

  65. Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafre SA et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem 2007; 282: 23716–23724.

    CAS  PubMed  Google Scholar 

  66. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005; 353: 1793–1801.

    CAS  PubMed  Google Scholar 

  67. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sc USA 2005; 102: 13944–13949.

    CAS  Google Scholar 

  68. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sc USA 2002; 99: 15524–15529.

    CAS  Google Scholar 

  69. Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A, Young BD . MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia 2007; 21: 912–916.

    CAS  PubMed  Google Scholar 

  70. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood 1998; 91: 3379–3389.

    CAS  PubMed  Google Scholar 

  71. Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M et al. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 2006; 8: 278–284.

    CAS  PubMed  Google Scholar 

  72. Akao Y, Nakagawa Y, Kitade Y, Kinoshita T, Naoe T . Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci 2007; 98: 1914–1920.

    CAS  PubMed  Google Scholar 

  73. Gauwerky CE, Huebner K, Isobe M, Nowell PC, Croce CM . Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. Proc Natl Acad Sci USA 1989; 86: 8867–8871.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ng D, Toure O, Wei MH, Arthur DC, Abbasi F, Fontaine L et al. Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia. Blood 2007; 109: 916–925.

    CAS  PubMed  Google Scholar 

  75. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006; 103: 2257–2261.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Tam W, Hughes SH, Hayward WS, Besmer P . Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol 2002; 76: 4275–4286.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Tam W . Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. Gene 2001; 274: 157–167.

    CAS  PubMed  Google Scholar 

  78. Yanaihara N, Caplen N, Bowman E, Kumamoto K, Okamoto A, Yokota J et al. MicroRNA signature in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9: 189–198.

    CAS  PubMed  Google Scholar 

  79. Marton S, Garcia MR, Robello C, Persson H, Trajtenberg F, Pritsch O et al. Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia 2007; 22: 330–338.

    PubMed  Google Scholar 

  80. Kluiver J, van den Berg A, de Jong D, Blokzijl T, Harms G, Bouwman E . et al. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene 2007; 26: 3769–3776.

    CAS  PubMed  Google Scholar 

  81. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D . MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007; 104: 1604–1609.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 2004; 64: 3087–3095.

    CAS  PubMed  Google Scholar 

  83. Cui JW, Li YJ, Sarkar A, Brown J, Tan YH, Premyslova M et al. Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation. Blood 2007; 110: 2631–2640.

    CAS  PubMed  Google Scholar 

  84. Venturini L, Battmer K, Castoldi M, Schultheis B, Hochhaus A, Muckenthaler MU et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood 2007; 109: 4399–4405.

    CAS  PubMed  Google Scholar 

  85. Bracken AP, Ciro M, Cocito A, Helin K . E2F target genes: unraveling the biology. Trends Biochem Sci 2004; 29: 409–417.

    CAS  PubMed  Google Scholar 

  86. Matsumura I, Tanaka H, Kanakura Y . E2F1 and c-Myc in cell growth and death. Cell Cycle 2003; 2: 333–338.

    CAS  PubMed  Google Scholar 

  87. Leone G, DeGregori J, Sears R, Jakoi L, Nevins JR . Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Nature 1997; 387: 422–426.

    CAS  PubMed  Google Scholar 

  88. Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J et al. Genomic targets of the human c-Myc protein. Genes Dev 2003; 17: 1115–1129.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Fabbri M, Ivan M, Cimmino A, Negrini M, Calin GA . Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther 2007; 7: 1009–1019.

    CAS  PubMed  Google Scholar 

  90. Landais S, Landry S, Legault P, Rassart E . Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia. Cancer Res 2007; 67: 5699–5707.

    CAS  PubMed  Google Scholar 

  91. Zanette DL, Rivadavia F, Molfetta GA, Barbuzano FG, Proto-Siqueira R, Falcao RP et al. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res 2007; 40: 1435–1440.

    CAS  PubMed  Google Scholar 

  92. Bullrich F, Fujii H, Calin G, Mabuchi H, Negrini M, Pekarsky Y et al. Characterization of the 13q14 tumor suppressor locus in CLL: identification of ALT1, an alternative splice variant of the LEU2 gene. Cancer Res 2001; 61: 6640–6648.

    CAS  PubMed  Google Scholar 

  93. Calin GA, Croce CM . Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol 2006; 33: 167–173.

    CAS  PubMed  Google Scholar 

  94. Adachi M, Tefferi A, Greipp PR, Kipps TJ, Tsujimoto Y . Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia. J Exp Med 1990; 171: 559–564.

    CAS  PubMed  Google Scholar 

  95. Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR et al. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 2007; 27: 2240–2252.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Pfeifer D, Pantic M, Skatulla I, Rawluk J, Kreutz C, Martens UM et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood 2007; 109: 1202–1210.

    CAS  PubMed  Google Scholar 

  97. Herling M, Patel KA, Khalili J, Schlette E, Kobayashi R, Medeiros LJ et al. TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state. Leukemia 2006; 20: 280–285.

    CAS  PubMed  Google Scholar 

  98. Pekarsky Y, Koval A, Hallas C, Bichi R, Tresini M, Malstrom S et al. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci USA 2000; 97: 3028–3033.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Laine J, Kunstle G, Obata T, Sha M, Noguchi M . The protooncogene TCL1 is an Akt kinase coactivator. Mol Cell 2000; 6: 395–407.

    CAS  PubMed  Google Scholar 

  100. Chan TO, Rittenhouse SE, Tsichlis PN . AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 1999; 68: 965–1014.

    CAS  PubMed  Google Scholar 

  101. Yan XJ, Albesiano E, Zanesi N, Yancopoulos S, Sawyer A, Romano E et al. B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2006; 103: 11713–11718.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Garzon R, Pichiorri F, Palumbo T, Visentini M, Aqeilan R, Cimmino A et al. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene 2007; 26: 4148–4157.

    CAS  PubMed  Google Scholar 

  103. Akao Y, Nakagawa Y, Naoe T . MicroRNA-143 and -145 in colon cancer. DNA Cell Biol 2007; 26: 311–320.

    CAS  PubMed  Google Scholar 

  104. Nishimoto S, Nishida E . MAPK signalling: ERK5 versus ERK1/2. EMBO Rep 2006; 7: 782–786.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834–838.

    CAS  PubMed  Google Scholar 

  106. Takada S, Mano H . Profiling of microRNA expression by mRAP. Nat Protoc 2007; 2: 3136–3145.

    CAS  PubMed  Google Scholar 

  107. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT et al. Real-time quantification of microRNAs by stem-loop RT–PCR. Nucleic Acids Res 2005; 33: e179.

    PubMed  PubMed Central  Google Scholar 

  108. Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA 2007; 104: 19971–19976.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L et al. Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell 2007; 12: 457–466.

    CAS  PubMed  Google Scholar 

  110. Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 2008. (E-pub ahead of print).

  111. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: 275–282.

    CAS  PubMed  Google Scholar 

  112. van den Berg A, Kroesen BJ, Kooistra K, de Jong D, Briggs J, Blokzijl T et al. High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer 2003; 37: 20–28.

    CAS  PubMed  Google Scholar 

  113. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005; 438: 685–689.

    PubMed  Google Scholar 

  114. Weiler J, Hunziker J, Hall J . Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Therapy 2005; 13: 496–502.

    Google Scholar 

  115. Orom UA, Kauppinen S, Lund AH . LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 2006; 372: 137–141.

    CAS  PubMed  Google Scholar 

  116. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT et al. Involvement of human microRNAs in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006; 130: 2113–2129.

    CAS  PubMed  Google Scholar 

  117. Hebert C, Norris K, Scheper MA, Nikitakis N, Sauk JJ . High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer 2007; 6: 5.

    PubMed  PubMed Central  Google Scholar 

  118. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA et al. Specific activation of microRNAs-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 2006; 9: 435–443.

    CAS  PubMed  Google Scholar 

  119. Pogribny IP, Tryndyak VP, Boyko A, Rodriguez-Juarez R, Beland FA, Kovalchuk O . Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure. Mutat Res 2007; 619: 30–37.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Dr Calin is supported by an MD Anderson Trust grant and by a Regent scholarship and by the CLL Global Research Foundation. We apologize to our colleagues whose work was not cited due to space limitations.

Author information

Authors and Affiliations

  1. Human Cancer Genetics, Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH, USA

    M Fabbri

  2. Department of Medicine, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA

    R Garzon

  3. Department of Stem Cell Transplantation and Cellular Therapies, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    M Andreeff

  4. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H M Kantarjian

  5. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    G Garcia-Manero & G A Calin

  6. Department of Cancer Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    G A Calin

Authors
  1. M Fabbri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Garzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Andreeff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H M Kantarjian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Garcia-Manero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G A Calin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G A Calin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fabbri, M., Garzon, R., Andreeff, M. et al. MicroRNAs and noncoding RNAs in hematological malignancies: molecular, clinical and therapeutic implications. Leukemia 22, 1095–1105 (2008). https://doi.org/10.1038/leu.2008.30

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2008.30

Keywords

This article is cited by

Search

Advanced search

Quick links