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miR Deregulation in CLL

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Advances in Chronic Lymphocytic Leukemia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 792))

Abstract

B-cell chronic lymphocytic leukemia (CLL) is the most frequent human leukemia and it occurs in two forms, indolent and aggressive. Although clinical features and genetic abnormalities in CLL are well documented, molecular details underlying the disease are still under investigation.

MicroRNAs are small noncoding RNAs involved in a variety of cellular processes and expressed in a tissue-specific manner. MicroRNAs have the ability to regulate gene expression. In physiological conditions, microRNAs act as gene expression controllers by targeting the mRNA or inhibiting its translation. Their deregulation can lead to an alteration of the expression level of many genes which can induce the development or promote the progression of tumors.

In CLL, microRNAs can function as oncogenes, tumor suppressor genes, and/or can be used as markers for disease onset/progression. For example, in indolent CLL, 13q14 deletions targeting miR-15/16 initiate the disease, while in aggressive CLL miR-181 targets the critical TCL1 oncogene and can also be used as a progression marker.

Here we discuss the foremost findings about the role of microRNAs in CLL pathogenesis, and how this knowledge can be used to identify new approaches to treat CLL.

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References

  1. Adachi M, Tefferi A, Greipp PR, et al. Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia. J Exp Med. 1990;171(2):559–64.

    Article  PubMed  CAS  Google Scholar 

  2. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113(6):673–6.

    Article  PubMed  CAS  Google Scholar 

  3. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5.

    Article  PubMed  CAS  Google Scholar 

  4. Asslaber D, Pinon JD, Seyfried I, et al. MicroRNA-34a expression correlates with MDM2 SNP309 polymorphism and treatment-free survival in chronic lymphocytic leukemia. Blood. 2010;115(21):4191–7.

    Article  PubMed  CAS  Google Scholar 

  5. Auer RL, Riaz S, Cotter FE. The 13q and 11q B-cell chronic lymphocytic leukaemia-associated regions derive from a common ancestral region in the zebrafish. Br J Haematol. 2007;137(5):443–53.

    Article  PubMed  CAS  Google Scholar 

  6. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  PubMed  CAS  Google Scholar 

  7. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996;274(5288):782–4.

    Article  PubMed  CAS  Google Scholar 

  8. Berland R, Wortis HH. An NFAT-dependent enhancer is necessary for anti-IgM-mediated induction of murine CD5 expression in primary splenic B cells. J Immunol. 1998;161(1):277–85.

    PubMed  CAS  Google Scholar 

  9. Bichi R, Shinton SA, Martin ES, et al. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc Natl Acad Sci U S A. 2002;99(10):6955–60.

    Article  PubMed  CAS  Google Scholar 

  10. Bommer GT, Gerin I, Feng Y, et al. p53-Mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17(15):1298–307.

    Article  PubMed  CAS  Google Scholar 

  11. Brockman JA, Scherer DC, McKinsey TA, et al. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. Mol Cell Biol. 1995;15(5):2809–18.

    PubMed  CAS  Google Scholar 

  12. Bullrich F, Croce CM. Molecular biology of chronic lymphocytic leukemia. In: Cheson B, editor. Chronic lymphocytic leukemias, 2nd ed, revised and expanded. New York: Marcel Dekker; 2001. p. 9–32.

    Google Scholar 

  13. Bullrich F, Fujii H, Calin G, 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(18):6640–8.

    PubMed  CAS  Google Scholar 

  14. Cai X, Hagedorn CH, Cullen BR. Human micrornas are processed from capped, polyadenylated transcripts that can also function as mrnas. RNA. 2004;10:1957–66.

    Article  PubMed  CAS  Google Scholar 

  15. Calin GA, Cimmino A, Fabbri M, et al. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008;105(13):5166–71.

    Article  PubMed  CAS  Google Scholar 

  16. Calin GA, Dumitru CD, Shimizu M, et al. 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. 2002;99(24):15524–9.

    Article  PubMed  CAS  Google Scholar 

  17. Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353(17):1793–801.

    Article  PubMed  CAS  Google Scholar 

  18. Calin GA, Liu CG, Sevignani C, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004;101(32):11755–60.

    Article  PubMed  CAS  Google Scholar 

  19. Calin GA, Pekarsky Y, Croce CM. The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007;20(3):425–37.

    Article  PubMed  CAS  Google Scholar 

  20. Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745–52.

    Article  PubMed  CAS  Google Scholar 

  21. Chen Z, Hagler J, Palombella VJ, et al. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 1995;9(13):1586–97.

    Article  PubMed  CAS  Google Scholar 

  22. Chiorazzi N. Cell proliferation and death: forgotten features of chronic lymphocytic leukemia B cells. Best Pract Res Clin Haematol. 2007;20(3):399–413.

    Article  PubMed  CAS  Google Scholar 

  23. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352(8):804–15.

    Article  PubMed  CAS  Google Scholar 

  24. Chung JY, Park YC, Ye H, et al. All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci. 2002;115(Pt 4):679–88.

    PubMed  CAS  Google Scholar 

  25. Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944–9.

    Article  PubMed  CAS  Google Scholar 

  26. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2(9):647–56.

    Article  PubMed  CAS  Google Scholar 

  27. Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1799–801.

    Article  PubMed  CAS  Google Scholar 

  28. Dijkstra MK, van Lom K, Tielemans D, et al. 17p13/TP53 deletion in B-CLL patients is associated with microRNA-34a downregulation. Leukemia. 2009;23(3):625–7.

    Article  PubMed  CAS  Google Scholar 

  29. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910–6.

    Article  PubMed  CAS  Google Scholar 

  30. Efanov A, Zanesi N, Nazaryan N, et al. CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation. Leukemia. 2010;24(5):970–5.

    Article  PubMed  CAS  Google Scholar 

  31. Fabbri M, Bottoni A, Shimizu M, et al. Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA. 2011;305(1):59–67.

    Article  PubMed  CAS  Google Scholar 

  32. Fabbri M, Ivan M, Cimmino A, et al. Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther. 2007;7(7):1009–19.

    Article  PubMed  CAS  Google Scholar 

  33. Ferracin M, Zagatti B, Rizzotto L, et al. MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Mol Cancer. 2010;26(9):123.

    Article  Google Scholar 

  34. Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225–60.

    Article  PubMed  CAS  Google Scholar 

  35. Gryshchenko I, Hofbauer S, Stoecher M, et al. MDM2 SNP309 is associated with poor outcome in B-cell chronic lymphocytic leukemia. J Clin Oncol. 2008;26(14):2252–7.

    Article  PubMed  CAS  Google Scholar 

  36. Haiat S, Billard C, Quiney C, et al. Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia. Immunology. 2006;118(3):281–92.

    Article  PubMed  CAS  Google Scholar 

  37. Hammarsund M, Corcoran MM, Wilson W, et al. Characterization of a novel B-CLL candidate gene–DLEU7–located in the 13q14 tumor suppressor locus. FEBS Lett. 2004;556(1–3):75–80.

    Article  PubMed  CAS  Google Scholar 

  38. Harfe BD. MicroRNAs in vertebrate development. Curr Opin Genet Dev. 2005;15:410–5.

    Article  PubMed  CAS  Google Scholar 

  39. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–4.

    Article  PubMed  CAS  Google Scholar 

  40. Herling M, Patel KA, Khalili J, et al. TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state. Leukemia. 2006;20(2):280–5.

    Article  PubMed  CAS  Google Scholar 

  41. Iorio MV, Croce CM. MicroRNA involvement in human cancer. Carcinogenesis. 2012;33(6):1126–33.

    Article  PubMed  CAS  Google Scholar 

  42. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.

    Article  PubMed  Google Scholar 

  43. Katsumata M, Siegel RM, Louie DC, et al. Differential effects of Bcl-2 on T and B cells in transgenic mice. Proc Natl Acad Sci U S A. 1992;89(23):11376–80.

    Article  PubMed  CAS  Google Scholar 

  44. Kitada S, Andersen J, Akar S, et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood. 1998;91(9):3379–89.

    PubMed  CAS  Google Scholar 

  45. Klein U, Lia M, Crespo M, et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell. 2010;17(1):28–40.

    Article  PubMed  CAS  Google Scholar 

  46. Laine J, Kunstle G, Obata T, et al. The protooncogene TCL1 is an Akt kinase coactivator. Mol Cell. 2000;6(2):395–407.

    Article  PubMed  CAS  Google Scholar 

  47. Lee SY, Reichlin A, Santana A, et al. TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival. Immunity. 1997;7(5):703–13.

    Article  PubMed  CAS  Google Scholar 

  48. Mackay F, Schneider P, Rennert P, et al. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–64.

    Article  PubMed  CAS  Google Scholar 

  49. Menin C, Scaini MC, De Salvo GL, et al. Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst. 2006;98(4):285–8.

    Article  PubMed  CAS  Google Scholar 

  50. Merkel O, Asslaber D, Pinon JD, et al. Interdependent regulation of p53 and miR-34a in chronic lymphocytic leukemia. Cell Cycle. 2010;9(14):2764–8.

    Article  PubMed  CAS  Google Scholar 

  51. Mertens D, Wolf S, Schroeter P, et al. Down-regulation of candidate tumor suppressor genes within chromosome band 13q14.3 is independent of the DNA methylation pattern in B-cell chronic lymphocytic leukemia. Blood. 2002;99(11):4116–21.

    Article  PubMed  CAS  Google Scholar 

  52. Messmer BT, Messmer D, Allen SL, et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest. 2005;115(3):755–64.

    PubMed  CAS  Google Scholar 

  53. Migliazza A, Bosch F, Komatsu H, et al. Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia. Blood. 2001;97(7):2098–104.

    Article  PubMed  CAS  Google Scholar 

  54. Moreno C, Montserrat E. Genetic lesions in chronic lymphocytic leukemia: what’s ready for prime time use? Haematologica. 2010;95(1):12–5.

    Article  PubMed  CAS  Google Scholar 

  55. Mraz M, Malinova K, Kotaskova J, et al. miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities. Leukemia. 2009;23(6):1159–63.

    Article  PubMed  CAS  Google Scholar 

  56. Neilson JR, Auer R, White D, et al. Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival. Leukemia. 1997;11(11):1929–32.

    Article  PubMed  CAS  Google Scholar 

  57. Ohmiya N, Taguchi A, Mabuchi N, et al. MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol. 2006;24(27):4434–40.

    Article  PubMed  CAS  Google Scholar 

  58. Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004;363(9403):105–11.

    Article  PubMed  CAS  Google Scholar 

  59. Ouillette P, Erba H, Kujawski L, et al. Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res. 2008;68(4):1012–21.

    Article  PubMed  CAS  Google Scholar 

  60. Palamarchuk A, Efanov A, Nazaryan N, et al. 13q14 deletions in CLL involve cooperating tumor suppressors. Blood. 2010;115(19):3916–22.

    Article  PubMed  CAS  Google Scholar 

  61. Palamarchuk A, Yan PS, Zanesi N, et al. Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL). Proc Natl Acad Sci U S A. 2012;109(7):2555–60.

    Article  PubMed  CAS  Google Scholar 

  62. Pekarsky Y, Calin GA, Aqeilan R. Chronic lymphocytic leukemia: molecular genetics and animal models. Curr Top Microbiol Immunol. 2005;294:51–70.

    Article  PubMed  CAS  Google Scholar 

  63. Pekarsky Y, Croce CM. Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget. 2010;1(3):224–7.

    PubMed  Google Scholar 

  64. Pekarsky Y, Koval A, Hallas C, et al. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci U S A. 2000;97(7):3028–33.

    Article  PubMed  CAS  Google Scholar 

  65. Pekarsky Y, Palamarchuk A, Maximov V, et al. Tcl1 functions as a transcriptional regulator and is directly involved in the pathogenesis of CLL. Proc Natl Acad Sci U S A. 2008;105(50):19643–8.

    Article  PubMed  CAS  Google Scholar 

  66. Pekarsky Y, Santanam U, Cimmino A, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66(24):11590–3.

    Article  PubMed  CAS  Google Scholar 

  67. Pekarsky Y, Zanesi N, Aqeilan RI, et al. Animal models for chronic lymphocytic leukemia. J Cell Biochem. 2007;100(5):1109–18.

    Article  PubMed  CAS  Google Scholar 

  68. Planelles L, Carvalho-Pinto CE, Hardenberg G, et al. APRIL promotes B-1 cell-associated neoplasm. Cancer Cell. 2004;6(4):399–408.

    Article  PubMed  CAS  Google Scholar 

  69. Ramkissoon SH, Mainwaring LA, Ogasawara Y, et al. Hematopoietic-specific microRNA expression in human cells. Leuk Res. 2006;30(5):643–7.

    Article  PubMed  CAS  Google Scholar 

  70. Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004;351(9):893–901.

    Article  PubMed  CAS  Google Scholar 

  71. Raveche ES. Possible immunoregulatory role for CD5+ B cells. Clin Immunol Immunopathol. 1990;56(2):135–50.

    Article  PubMed  CAS  Google Scholar 

  72. Raveche ES, Salerno E, Scaglione BJ, et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood. 2007;109(12):5079–86.

    Article  PubMed  CAS  Google Scholar 

  73. Rondeau G, Moreau I, Bezieau S, et al. Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus. Mutat Res. 2001;458(3–4):55–70.

    PubMed  CAS  Google Scholar 

  74. Rossi S, Shimizu M, Barbarotto E, et al. MicroRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116(6):945–52.

    Article  PubMed  CAS  Google Scholar 

  75. Sampath D, Liu C, Vasan K, et al. Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. Blood. 2012;119(5):1162–72.

    Article  PubMed  CAS  Google Scholar 

  76. Sanchez-Beato M, Sanchez-Aguilera A, Piris MA. Cell cycle deregulation in B-cell lymphomas. Blood. 2003;101(4):1220–35.

    Article  PubMed  CAS  Google Scholar 

  77. Santanam U, Zanesi N, Efanov A, et al. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A. 2010;107(27):12210–5.

    Article  PubMed  CAS  Google Scholar 

  78. Schuh K, Avots A, Tony HP, et al. Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients. Leuk Lymphoma. 1996;23(5–6):583–92.

    Article  PubMed  CAS  Google Scholar 

  79. Sieklucka M, Pozarowski P, Bojarska-Junak A, et al. Apoptosis in B-CLL: the relationship between higher ex vivo spontaneous apoptosis before treatment in III-IV Rai stage patients and poor outcome. Oncol Rep. 2008;19(6):1611–20.

    PubMed  CAS  Google Scholar 

  80. Smonskey MT, Block AW, Deeb G, et al. Monoallelic and biallelic deletions of 13q14.3 in chronic lymphocytic leukemia: FISH vs miRNA RT-qPCR detection. Am J Clin Pathol. 2012;137:641–6.

    Article  PubMed  Google Scholar 

  81. Stilgenbauer S, Bullinger L, Benner A, et al. Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia. 1999;13(9):1331–4.

    Article  PubMed  CAS  Google Scholar 

  82. Tarasov V, Jung P, Verdoodt B, et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 2007;6(13):1586–93.

    Article  PubMed  CAS  Google Scholar 

  83. Tsujimoto Y, Cossman J, Jaffe E, et al. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985;228(4706):1440–3.

    Article  PubMed  CAS  Google Scholar 

  84. Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9.

    Article  PubMed  CAS  Google Scholar 

  85. Van Antwerp DJ, Martin SJ, Kafri T, et al. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science. 1996;274(5288):787–9.

    Article  PubMed  Google Scholar 

  86. van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet. 1999;23(4):474–8.

    Article  PubMed  Google Scholar 

  87. Virgilio L, Narducci MG, Isobe M, et al. Identification of the TCL1 gene involved in T-cell malignancies. Proc Natl Acad Sci U S A. 1994;91(26):12530–4.

    Article  PubMed  CAS  Google Scholar 

  88. Visone R, Rassenti LZ, Veronese A, et al. Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood. 2009;114(18):3872–9.

    Article  PubMed  CAS  Google Scholar 

  89. Visone R, Veronese A, Rassenti LZ, et al. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood. 2011;118(11):3072–9.

    Article  PubMed  CAS  Google Scholar 

  90. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61.

    Article  PubMed  CAS  Google Scholar 

  91. Wang CY, Mayo MW, Baldwin Jr AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274(5288):784–7.

    Article  PubMed  CAS  Google Scholar 

  92. Wolf S, Mertens D, Schaffner C, et al. B-cell neoplasia associated gene with multiple splicing (BCMS): the candidate B-CLL gene on 13q14 comprises more than 560 kb covering all critical regions. Hum Mol Genet. 2001;10(12):1275–85.

    Article  PubMed  CAS  Google Scholar 

  93. Zanesi N, Pekarsky Y, Trapasso F, et al. MicroRNAs in mouse models of lymphoid malignancies. J Nucleic Acids Investig. 2010;1(1):36–40.

    PubMed  CAS  Google Scholar 

  94. Zapata JM, Krajewska M, Morse 3rd HC, et al. TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice. Proc Natl Acad Sci U S A. 2004;101(47):16600–5.

    Article  PubMed  CAS  Google Scholar 

  95. Zenz T, Mertens D, Dohner H, et al. Molecular diagnostics in chronic lymphocytic leukemia—pathogenetic and clinical implications. Leuk Lymphoma. 2008;49(5):864–73.

    Article  PubMed  CAS  Google Scholar 

  96. Zenz T, Mohr J, Eldering E, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009;113(16):3801–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by ACS Research Scholar Award, Swan Family Award, and CLL Global Foundation (to Y. Pekarsky).

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Authors and Affiliations

  1. Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center and the Wexner Medical Center, The Ohio State University, Columbus, OH, USA

    Veronica Balatti, Yuri Pekarky, Lara Rizzotto & Carlo M. Croce

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  1. Veronica Balatti
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  2. Yuri Pekarky
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  4. Carlo M. Croce
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Correspondence to Carlo M. Croce .

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  1. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Sami Malek

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Balatti, V., Pekarky, Y., Rizzotto, L., Croce, C.M. (2013). miR Deregulation in CLL. In: Malek, S. (eds) Advances in Chronic Lymphocytic Leukemia. Advances in Experimental Medicine and Biology, vol 792. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8051-8_14

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