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MicroRNA in Leukemias

  • Deepa SampathEmail author
Chapter

Abstract

MicroRNAs are a class of master gene regulators that are extensively deregulated in all leukemias. Distinctive miRNA signatures are expressed in each cytogenetically defined subtype of leukemia which play multifaceted roles in the genesis, pathobiology, progression and clinical outcome of this group of diseases. This chapter aims to provide a comprehensive review of the expression, regulation and cellular targets of the microRNAs in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) in order to understand the regulatory role of microRNA in the leukemias as well as to identify novel therapeutic targets.

Keywords

Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia miRNA Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Agirre X, Vilas-Zornoza A, Jimenez-Velasco A, Martin-Subero JI, Cordeu L, Garate L, San Jose-Eneriz E, Abizanda G, Rodriguez-Otero P, Fortes P et al (2009) Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res 69:4443–4453PubMedCrossRefGoogle Scholar
  2. 2.
    Asslaber D, Pinon JD, Seyfried I, Desch P, Stocher M, Tinhofer I, Egle A, Merkel O, Greil R (2010) MicroRNA-34a expression correlates with MDM2 SNP309 polymorphism and treatment-free survival in chronic lymphocytic leukemia. Blood 115:4191–4197PubMedCrossRefGoogle Scholar
  3. 3.
    Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–71PubMedCrossRefGoogle Scholar
  4. 4.
    Baldus CD, Martus P, Burmeister T, Schwartz S, Gokbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK (2007) Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J Clin Oncol 25:3739–3745PubMedCrossRefGoogle Scholar
  5. 5.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233PubMedCrossRefGoogle Scholar
  6. 6.
    Bartel DP, Chen CZ (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5:396–400PubMedCrossRefGoogle Scholar
  7. 7.
    Becker H, Marcucci G, Maharry K, Radmacher MD, Mrozek K, Margeson D, Whitman SP, Wu YZ, Schwind S, Paschka P et al (2010) Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 28:596–604PubMedCrossRefGoogle Scholar
  8. 8.
    Bhatia S, Kaul D, Varma N (2010) Potential tumor suppressive function of miR-196b in B-cell lineage acute lymphoblastic leukemia. Mol Cell Biochem 340:97–106Google Scholar
  9. 9.
    Bhatia S, Kaul D, Varma N (2011) Functional genomics of tumor suppressor miR-196b in T-cell acute lymphoblastic leukemia. Mol Cell Biochem 346:103–116PubMedCrossRefGoogle Scholar
  10. 10.
    Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L et al (2010) Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A 107:7473–7478PubMedCrossRefGoogle Scholar
  11. 11.
    Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C et al (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277PubMedCrossRefGoogle Scholar
  12. 12.
    Bousquet M, Harris MH, Zhou B, Lodish HF MicroRNA miR-125b causes leukemia. Proc Natl Acad Sci U S A 107:21558–21563Google Scholar
  13. 13.
    Brioschi M, Fischer J, Cairoli R, Rossetti S, Pezzetti L, Nichelatti M, Turrini M, Corlazzoli F, Scarpati B, Morra E et al (2010) Down-regulation of microRNAs 222/221 in acute myelogenous leukemia with deranged core-binding factor subunits. Neoplasia 12:866–876PubMedGoogle Scholar
  14. 14.
    Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernandez-Piqueras J, Malumbres M (2008) Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 13:496–506PubMedCrossRefGoogle Scholar
  15. 15.
    Calin GA, Croce CM (2006a) Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol 33:167–173CrossRefGoogle Scholar
  16. 16.
    Calin GA, Croce CM (2006b) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866CrossRefGoogle Scholar
  17. 17.
    Calin GA, Croce CM (2006c) MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 25:6202–6210CrossRefGoogle Scholar
  18. 18.
    Calin GA, Croce CM (2007) Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest 117:2059–2066PubMedCrossRefGoogle Scholar
  19. 19.
    Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529PubMedCrossRefGoogle Scholar
  20. 20.
    Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M et al (2004a) MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A 101:11755–11760CrossRefGoogle Scholar
  21. 21.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M et al (2004b) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004CrossRefGoogle Scholar
  22. 22.
    Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M et al (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353:1793–1801PubMedCrossRefGoogle Scholar
  23. 23.
    Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI et al (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A 105:5166–5171PubMedCrossRefGoogle Scholar
  24. 24.
    Cammarata G, Augugliaro L, Salemi D, Agueli C, La Rosa M, Dagnino L, Civiletto G, Messana F, Marfia A, Bica MG et al (2010) Differential expression of specific microRNA and their targets in acute myeloid leukemia. Am J Hematol 85:331–339PubMedGoogle Scholar
  25. 25.
    Carella C, Bonten J, Sirma S, Kranenburg TA, Terranova S, Klein-Geltink R, Shurtleff S, Downing JR, Zwarthoff EC, Liu PP et al (2007) MN1 overexpression is an important step in the development of inv(16) AML. Leukemia 21:1679–1690PubMedCrossRefGoogle Scholar
  26. 26.
    Chandra P, Luthra R, Zuo Z, Yao H, Ravandi F, Reddy N, Garcia-Manero G, Kantarjian H, Jones D (2010) Acute myeloid leukemia with t(9;11)(p21–22;q23): common properties of dysregulated ras pathway signaling and genomic progression characterize de novo and therapy-related cases. Am J Clin Pathol 133:686–693PubMedCrossRefGoogle Scholar
  27. 27.
    Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745–752PubMedCrossRefGoogle Scholar
  28. 28.
    Chapiro E, Russell LJ, Struski S, Cave H, Radford-Weiss I, Valle VD, Lachenaud J, Brousset P, Bernard OA, Harrison CJ et al 2010 A new recurrent translocation t(11;14)(q24;q32) involving IGH@ and miR-125b-1 in B-cell progenitor acute lymphoblastic leukemia. Leukemia 24:1362–1364Google Scholar
  29. 29.
    Chase A, Huntly BJ, Cross NC (2001) Cytogenetics of chronic myeloid leukaemia. Best Pract Res Clin Haematol 14:553–571PubMedCrossRefGoogle Scholar
  30. 30.
    Chim CS, Wong AS Kwong YL (2005) Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias. Am J Hematol 80:282–287PubMedCrossRefGoogle Scholar
  31. 31.
    Chim CS, Wong KY, Qi Y, Loong F, Lam WL, Wong LG, Jin DY, Costello JF, Liang R (2010) Epigenetic inactivation of the miR-34a in hematological malignancies. Carcinogenesis 31:745–750PubMedCrossRefGoogle Scholar
  32. 32.
    Chim CS, Wong KY, Leung CY, Chung LP, Hui PK, Chan SY, Yu L (2011a) Epigenetic inactivation of the hsa-miR-203 in haematological malignancies. J Cell Mol Med 15(12):2760–2767Google Scholar
  33. 33.
    Chim CS, Wong KY, Qi Y, Loong F, Lam WL, Wong LG, Jin DY, Costello JF, Liang R (2011b) Epigenetic inactivation of the miR-34a in hematological malignancies. Carcinogenesis 31:745–750CrossRefGoogle Scholar
  34. 34.
    Chuang JC, Jones PA (2007) Epigenetics and microRNAs. Pediatr Res 61:24R-29RPubMedCrossRefGoogle Scholar
  35. 35.
    Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102:13944–13949PubMedCrossRefGoogle Scholar
  36. 36.
    Coskun E, von der Heide EK, Schlee C, Kuhnl A, Gokbuget N, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2011) The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia. Leuk Res 35:208–213PubMedCrossRefGoogle Scholar
  37. 37.
    Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714PubMedCrossRefGoogle Scholar
  38. 38.
    Davidsson J, Lilljebjorn H, Andersson A, Veerla S, Heldrup J, Behrendtz M, Fioretos T, Johansson B (2009) The DNA methylome of pediatric acute lymphoblastic leukemia. Hum Mol Genet 18:4054–4065PubMedCrossRefGoogle Scholar
  39. 39.
    Dixon-McIver A, East P, Mein CA, Cazier JB, Molloy G, Chaplin T, Andrew Lister T, Young BD, Debernardi S (2008) Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One 3:e2141PubMedCrossRefGoogle Scholar
  40. 40.
    Ebert BL (2010) Genetic deletions in AML and MDS. Best Pract Res Clin Haematol 23:457–461PubMedCrossRefGoogle Scholar
  41. 41.
    Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ et al (2010) miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140:652–665PubMedCrossRefGoogle Scholar
  42. 42.
    Eyholzer M, Schmid S, Wilkens L, Mueller BU, Pabst T (2010) The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML. Br J Cancer 103:275–284PubMedCrossRefGoogle Scholar
  43. 43.
    Fabbri M, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE et al (2011) Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA 305:59–67PubMedCrossRefGoogle Scholar
  44. 44.
    Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310:1817–1821PubMedCrossRefGoogle Scholar
  45. 45.
    Fatica A, Rosa A, Fazi F, Ballarino M, Morlando M, De Angelis FG, Caffarelli E, Nervi C, Bozzoni I (2006) MicroRNAs and hematopoietic differentiation. Cold Spring Harb Symp Quant Biol 71:205–210PubMedCrossRefGoogle Scholar
  46. 46.
    Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L, Diverio D, Ammatuna E, Cimino G, Lo-Coco F et al (2007) Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell 12:457–466PubMedCrossRefGoogle Scholar
  47. 47.
    Ferracin M, Zagatti B, Rizzotto L, Cavazzini F, Veronese A, Ciccone M, Saccenti E, Lupini L, Grilli A, De Angeli C et al (2010) MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Mol Cancer 9:123PubMedCrossRefGoogle Scholar
  48. 48.
    Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, Castellano L, Magrelli A, Citarella F, Messina M et al (2007) Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood 109:4944–4951PubMedCrossRefGoogle Scholar
  49. 49.
    Fulci V, Colombo T, Chiaretti S, Messina M, Citarella F, Tavolaro S, Guarini A, Foa R, Macino G (2009) Characterization of B- and T-lineage acute lymphoblastic leukemia by integrated analysis of MicroRNA and mRNA expression profiles. Genes Chromosomes Cancer 48:1069–1082PubMedCrossRefGoogle Scholar
  50. 50.
    Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T et al (2008a) Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 105:3945–3950CrossRefGoogle Scholar
  51. 51.
    Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, Fabbri M, Coombes K, Alder H, Nakamura T et al (2008b) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111:3183–3189CrossRefGoogle Scholar
  52. 52.
    Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA et al (2009a) MicroRNA 29b functions in acute myeloid leukemia. Blood 114:5331–5341CrossRefGoogle Scholar
  53. 53.
    Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA et al (2009b) MicroRNA 29b functions in acute myeloid leukemia. Blood 114(26):5331–5341.Google Scholar
  54. 54.
    Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N et al (2009c) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113:6411–6418CrossRefGoogle Scholar
  55. 55.
    Gefen N, Binder V, Zaliova M, Linka Y, Morrow M, Novosel A, Edry L, Hertzberg L, Shomron N, Williams O et al (2010) Hsa-mir-125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53. Leukemia 24:89–96Google Scholar
  56. 56.
    Grosveld GC (2007) MN1, a novel player in human AML. Blood Cells Mol Dis 39:336–339PubMedCrossRefGoogle Scholar
  57. 57.
    Hamblin TJ (2007) Prognostic markers in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 20:455–468PubMedCrossRefGoogle Scholar
  58. 58.
    Harrison CJ (2000) The genetics of childhood acute lymphoblastic leukaemia. Baillieres Best Pract Res Clin Haematol 13:427–439PubMedCrossRefGoogle Scholar
  59. 59.
    Herman JG, Jen J, Merlo A, Baylin SB (1996) Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res 56:722–727PubMedGoogle Scholar
  60. 60.
    Jima DD, Zhang J, Jacobs C, Richards KL, Dunphy CH, Choi WW, Yan Au W, Srivastava G, Czader MB, Rizzieri DA et al (2010) Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs. Blood 116, e118–127PubMedCrossRefGoogle Scholar
  61. 61.
    Jongen-Lavrencic M, Sun SM, Dijkstra MK, Valk PJ, Lowenberg B (2008) MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 111:5078–5085PubMedCrossRefGoogle Scholar
  62. 62.
    Ju X, Li D, Shi Q, Hou H, Sun N, Shen B (2009) Differential microRNA expression in childhood B-cell precursor acute lymphoblastic leukemia. Pediatr Hematol Oncol 26:1–10PubMedCrossRefGoogle Scholar
  63. 63.
    Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H, Sakashita A, Said J, Tatsumi E, Koeffler HP (1999) Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. Blood 94:1113–1120PubMedGoogle Scholar
  64. 64.
    Keating MJ, Chiorazzi N, Messmer B, Damle RN, Allen SL, Rai KR, Ferrarini M, Kipps TJ (2003) Biology and treatment of chronic lymphocytic leukemia. Hematology, American Society of Hematology Education Program Book Vol: 2003, No1, 153–175Google Scholar
  65. 65.
    Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, Ambesi-Impiombato A, Califano A, Migliazza A, Bhagat G et al (2010) The DLEU2/miR-15a/16-1 Cluster Controls B Cell Proliferation and Its Deletion Leads to Chronic Lymphocytic Leukemia. Cancer Cell 17(1):28-40Google Scholar
  66. 66.
    Langer C, Marcucci G, Holland KB, Radmacher MD, Maharry K, Paschka P, Whitman SP, Mrozek K, Baldus CD, Vij R et al (2009) Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol 27:3198–3204PubMedCrossRefGoogle Scholar
  67. 67.
    Langer C, Radmacher MD, Ruppert AS, Whitman SP, Paschka P, Mrozek K, Baldus CD, Vukosavljevic T, Liu CG, Ross ME et al (2008) High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 111:5371–5379PubMedCrossRefGoogle Scholar
  68. 68.
    Lerner M, Harada M, Loven J, Castro J, Davis Z, Oscier D, Henriksson M, Sangfelt O, Grander D, Corcoran MM (2009) DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1. Exp Cell Res 315:2941–2952PubMedCrossRefGoogle Scholar
  69. 69.
    Levitt L, Lin R (1996) Biology and treatment of adult acute lymphoblastic leukemia. West J Med 164:143–155PubMedGoogle Scholar
  70. 70.
    Li S, Moffett HF, Lu J, Werner L, Zhang H, Ritz J, Neuberg D, Wucherpfennig KW, Brown JR, Novina CD (2010a) MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One 6:e16956CrossRefGoogle Scholar
  71. 71.
    Li S, Moffett HF, Lu J, Werner L, Zhang H, Ritz J, Neuberg D, Wucherpfennig KW, Brown JR, Novina CD (2011) MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One 6:e16956PubMedCrossRefGoogle Scholar
  72. 72.
    Li X, Liu J, Zhou R, Huang S, Chen XM (2010b) Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation. Br J Haematol 148:69–79CrossRefGoogle Scholar
  73. 73.
    Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z et al (2008) Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci U S A 105:15535–15540PubMedCrossRefGoogle Scholar
  74. 74.
    Liu M, Taketani T, Li R, Takita J, Taki T, Yang HW, Kawaguchi H, Ida K, Matsuo Y, Hayashi Y (2001) Loss of p73 gene expression in lymphoid leukemia cell lines is associated with hypermethylation. Leuk Res 25:441–447PubMedCrossRefGoogle Scholar
  75. 75.
    Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K et al (2010) Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. Cancer Cell 17:333–347PubMedCrossRefGoogle Scholar
  76. 76.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838PubMedCrossRefGoogle Scholar
  77. 77.
    Machova Polakova K, Lopotova T, Klamova H, Burda P, Trneny M, Stopka T, Moravcova J (2011) Expression patterns of microRNAs associated with CML phases and their disease related targets. Mol Cancer 10:41CrossRefGoogle Scholar
  78. 78.
    Marcucci G, Maharry K, Radmacher MD, Mrozek K, Vukosavljevic T, Paschka P, Whitman SP, Langer C, Baldus CD, Liu, CG et al (2008a) Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clin Oncol 26:5078–5087CrossRefGoogle Scholar
  79. 79.
    Marcucci G, Radmacher MD, Maharry K, Mrozek K, Ruppert AS, Paschka P, Vukosavljevic T, Whitman SP, Baldus CD, Langer C et al (2008b) MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med 358:1919–1928CrossRefGoogle Scholar
  80. 80.
    Marcucci G, Radmacher MD, Mrozek K, Bloomfield, CD (2009) MicroRNA expression in acute myeloid leukemia. Curr Hematol Malig Rep 4:83–88PubMedCrossRefGoogle Scholar
  81. 81.
    Marcucci G, Haferlach T, Dohner, H (2011) Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 29:475–486PubMedCrossRefGoogle Scholar
  82. 82.
    Marton S, Garcia MR, Robello C, Persson H, Trajtenberg F, Pritsch O, Rovira C, Naya H, Dighiero G, Cayota, A (2008) Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia 22:330–338PubMedCrossRefGoogle Scholar
  83. 83.
    Matsushita C, Yang Y, Takeuchi S, Matsushita M, Van Dongen JJ, Szczepanski T, Bartram CR, Seo H, Koeffler HP, Taguchi, H (2004) Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia. Oncol Rep 12:97–99PubMedGoogle Scholar
  84. 84.
    Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K, McJunkin K, Zuber J, James T, Khan AA, Leslie, CS et al (2011) Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 12:372–379CrossRefGoogle Scholar
  85. 85.
    Mehes, G (2005) Chromosome abnormalities with prognostic impact in B-cell chronic lymphocytic leukemia. Pathol Oncol Res 11:205–210PubMedCrossRefGoogle Scholar
  86. 86.
    Mertens D, Philippen A, Ruppel M, Allegra D, Bhattacharya N, Tschuch C, Wolf S, Idler I, Zenz T, Stilgenbauer, S (2009) Chronic lymphocytic leukemia and 13q14: miRs and more. Leuk Lymphoma 50:502–505PubMedCrossRefGoogle Scholar
  87. 87.
    Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y et al (2007) MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci U S A 104:19971–19976PubMedCrossRefGoogle Scholar
  88. 88.
    Moussay E, Wang K, Cho JH, van Moer K, Pierson S, Paggetti J, Nazarov PV, Palissot V, Hood LE, Berchem G et al (2011) MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 108:6573–6578PubMedCrossRefGoogle Scholar
  89. 89.
    Mraz M, Malinova K, Kotaskova J, Pavlova S, Tichy B, Malcikova J, Stano Kozubik K, Smardova J, Brychtova Y, Doubek M et al (2009a) miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities. Leukemia 23:1159–1163CrossRefGoogle Scholar
  90. 90.
    Mraz M, Pospisilova S, Malinova K, Slapak I, Mayer, J (2009b) MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes. Leuk Lymphoma 50:506–509CrossRefGoogle Scholar
  91. 91.
    Mrozek, K (2008) Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype. Semin Oncol 35:365–377PubMedCrossRefGoogle Scholar
  92. 92.
    Mrozek K, Bloomfield, CD (2006) Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology, American Society of Hematology Education Program Book Vol: 2006, No1, 169–177Google Scholar
  93. 93.
    Mrozek K, Bloomfield, CD (2008) Clinical significance of the most common chromosome translocations in adult acute myeloid leukemia. J Natl Cancer Inst Monogr (39):52–57Google Scholar
  94. 94.
    Mrozek K, Heerema NA, Bloomfield, CD (2004) Cytogenetics in acute leukemia. Blood Rev 18:115–136PubMedCrossRefGoogle Scholar
  95. 95.
    Nagarajan, L (2010) Chromosomal deletions in AML. Cancer Treat Res 145:59–66PubMedCrossRefGoogle Scholar
  96. 96.
    Nagel S, Venturini L, Przybylski GK, Grabarczyk P, Schmidt CA, Meyer C, Drexler HG, Macleod RA, Scherr, M (2009) Activation of miR-17-92 by NK-like homeodomain proteins suppresses apoptosis via reduction of E2F1 in T-cell acute lymphoblastic leukemia. Leuk Lymphoma 50:101–108PubMedCrossRefGoogle Scholar
  97. 97.
    Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek, SN (2008) Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res 68:1012–1021PubMedCrossRefGoogle Scholar
  98. 98.
    Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE, Tenen, DG (2001a) AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med 7:444–451CrossRefGoogle Scholar
  99. 99.
    Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W, Tenen, DG (2001b) Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet 27:263–270CrossRefGoogle Scholar
  100. 100.
    Pallasch CP, Patz M, Park YJ, Hagist S, Eggle D, Claus R, Debey-Pascher S, Schulz A, Frenzel LP, Claasen J et al (2009) miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia. Blood 114:3255–3264PubMedCrossRefGoogle Scholar
  101. 101.
    Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L et al (2006) Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66:11590–11593PubMedCrossRefGoogle Scholar
  102. 102.
    Petrocca F, Vecchione A, Croce, CM (2008a) Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res 68:8191–8194CrossRefGoogle Scholar
  103. 103.
    Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu CG, Negrini M et al (2008b) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13:272–286CrossRefGoogle Scholar
  104. 104.
    Pulikkan JA, Peramangalam PS, Dengler V, Ho PA, Preudhomme C, Meshinchi S, Christopeit M, Nibourel O, Muller-Tidow C, Bohlander, SK et al (2010) C/EBPalpha regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood 116:5638–5649PubMedCrossRefGoogle Scholar
  105. 105.
    Rassenti LZ, Huynh L, Toy TL, Chen L, Keating MJ, Gribben JG, Neuberg DS, Flinn IW, Rai KR, Byrd, JC et al (2004) ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351:893–901PubMedCrossRefGoogle Scholar
  106. 106.
    Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K et al (2007) Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood 109:5079–5086PubMedCrossRefGoogle Scholar
  107. 107.
    Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26:731–743PubMedCrossRefGoogle Scholar
  108. 108.
    Reuss-Borst MA, Buhring HJ, Schmidt H, Muller, CA (1994) AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression. Leukemia 8:258–263PubMedGoogle Scholar
  109. 109.
    Roman-Gomez J, Jimenez-Velasco A, Barrios M, Prosper F, Heiniger A, Torres A, Agirre, X (2007) Poor prognosis in acute lymphoblastic leukemia may relate to promoter hypermethylation of cancer-related genes. Leuk Lymphoma 48:1269–1282PubMedCrossRefGoogle Scholar
  110. 110.
    Roman-Gomez J, Agirre X, Jiménez-Velasco A, Arqueros V, Vilas-Zornoza A, Rodriguez-Otero P, Martin-Subero I, Garate L, Cordeu L, San José-Eneriz E, Martin V, Castillejo JA, Bandrés E, Calasanz MJ, Siebert R, Heiniger A, Torres A, Prosper F (2009). Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. J Clin Oncol 27(8):1316-1322.Google Scholar
  111. 111.
    Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, Fabbri M, Lerner S, Barron LL, Rassenti, LZ et al (2010) microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood 116(6):945–952Google Scholar
  112. 112.
    Sampath D, Calin GA, Puduvalli VK, Gopisetty G, Taccioli C, Liu CG, Ewald B, Liu C, Keating MJ, Plunkett, W (2009) Specific activation of microRNA106b enables the p73 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation. Blood 113:3744–3753PubMedCrossRefGoogle Scholar
  113. 113.
    San Jose-Eneriz E, Roman-Gomez J, Jimenez-Velasco A, Garate L, Martin V, Cordeu L, Vilas-Zornoza A, Rodriguez-Otero P, Calasanz MJ, Prosper F et al (2009) MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations. Mol Cancer 8:69CrossRefGoogle Scholar
  114. 114.
    Santanam U, Zanesi N, Efanov A, Costinean S, Palamarchuk A, Hagan JP, Volinia S, Alder H, Rassenti L, Kipps T et al (2010) Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A 107:12210–12215PubMedCrossRefGoogle Scholar
  115. 115.
    Schotte D, Chau JC, Sylvester G, Liu G, Chen C, Van Der Velden VH, Broekhuis MJ, Peters TC, Pieters R, den Boer, ML (2009) Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia. Leukemia 23:313–322PubMedCrossRefGoogle Scholar
  116. 116.
    Schotte D, De Menezes RX, Moqadam FA, Khankahdani LM, Lange-Turenhout E, Chen C, Pieters R, Den Boer, ML (2011) MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica 96:703–711CrossRefGoogle Scholar
  117. 117.
    Schotte D, Moqadam FA, Lange-Turenhout EA, Chen C, van Ijcken WF, Pieters R, den Boer, ML (2011b) Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia. Leukemia Sep;25(9):1389-1399Google Scholar
  118. 118.
    Schwind S, Maharry K, Radmacher MD, Mrozek K, Holland KB, Margeson D, Whitman SP, Hickey C, Becker H, Metzeler, KH et al (2010a) Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 28:5257–5264CrossRefGoogle Scholar
  119. 119.
    Schwind S, Marcucci G, Maharry K, Radmacher MD, Mrozek K, Holland KB, Margeson D, Becker H, Whitman SP, Wu YZ et al (2010b) BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 116:5660–5669CrossRefGoogle Scholar
  120. 120.
    Shin C, Nam JW, Farh KK, Chiang HR, Shkumatava A, Bartel, DP (2010) Expanding the microRNA targeting code: functional sites with centered pairing. Mol Cell 38:789–802PubMedCrossRefGoogle Scholar
  121. 121.
    Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux, L (2009) microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood 113:5237–5245PubMedCrossRefGoogle Scholar
  122. 122.
    Stumpel DJ, Schotte D, Lange-Turenhout EA, Schneider P, Seslija L, de Menezes RX, Marquez VE, Pieters R, den Boer ML, Stam, RW (2011) Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia 25:429–439PubMedCrossRefGoogle Scholar
  123. 123.
    Suresh S, McCallum L, Lu W, Lazar N, Perbal B, Irvine, AE (2011) MicroRNAs 130a/b are regulated by BCR-ABL and downregulate expression of CCN3 in CML. J Cell Commun SignalGoogle Scholar
  124. 124.
    Visone R, Rassenti LZ, Veronese A, Taccioli C, Costinean S, Aguda BD, Volinia S, Ferracin M, Palatini J, Balatti V et al (2009) Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood 114:3872–3879PubMedCrossRefGoogle Scholar
  125. 125.
    Visone R, Veronese A, Rassenti LZ, Balatti V, Pearl DK, Acunzo M, Volinia S, Taccioli C, Kipps TJ, Croce, CM (2011) MiR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. BloodGoogle Scholar
  126. 126.
    Wattanawaraporn R, Singhsilarak T, Nuchprayoon I, Mutirangura, A (2007) Hypermethylation of TTC12 gene in acute lymphoblastic leukemia. Leukemia 21:2370–2373PubMedCrossRefGoogle Scholar
  127. 127.
    Whitman SP, Maharry K, Radmacher MD, Becker H, Mrozek K, Margeson D, Holland KB, Wu YZ, Schwind S, Metzeler, KH et al (2010) FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 116:3622–3626PubMedCrossRefGoogle Scholar
  128. 128.
    Zanette DL, Rivadavia F, Molfetta GA, Barbuzano FG, Proto-Siqueira R, Silva-Jr WA, Falcao RP, Zago, MA (2007) miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res 40:1435–1440PubMedCrossRefGoogle Scholar
  129. 129.
    Zenz T, Benner A, Dohner H, Stilgenbauer, S (2008) Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle 7:3810–3814PubMedCrossRefGoogle Scholar
  130. 130.
    Zenz T, Habe S, Denzel T, Mohr J, Winkler D, Buhler A, Sarno A, Groner S, Mertens D, Busch R et al (2009a) Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood 114:2589–2597CrossRefGoogle Scholar
  131. 131.
    Zenz T, Mohr J, Eldering E, Kater AP, Buhler A, Kienle D, Winkler D, Durig J, van Oers MH, Mertens D et al (2009b) miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood 113:3801–3808CrossRefGoogle Scholar
  132. 132.
    Zhang H, Yang JH, Zheng YS, Zhang P, Chen X, Wu J, Xu L, Luo XQ, Ke ZY, Zhou H et al (2009) Genome-wide analysis of small RNA and novel MicroRNA discovery in human acute lymphoblastic leukemia based on extensive sequencing approach. PLoS One 4:e6849PubMedCrossRefGoogle Scholar
  133. 133.
    Zhao JJ, Lin J, Lwin T, Yang H, Guo J, Kong W, Dessureault S, Moscinski LC, Rezania D, Dalton WS et al (2010) microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 115:2630–2639PubMedCrossRefGoogle Scholar
  134. 134.
    Zimmerman EI, Dollins CM, Crawford M, Grant S, Nana-Sinkam SP, Richards KL, Hammond SM, Graves LM (2010) Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression: implications for drug resistance in myelogenous leukemia. Mol Pharmacol 78:811–817PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Experimental TherapeuticsUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA

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