Advertisement

microRNA and Chronic Lymphocytic Leukemia

  • Dana Elena Giza
  • George A. CalinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 889)

Abstract

Expression profiling of microRNAs identified important differences in microRNA expression between CLL samples and normal CD5+ B-cells. Researchers have first discussed the dual role of miRNAs working as tumor suppressors (inhibiting malignant potential) or as oncogenes (activating malignant potential) in CLL pathogenesis. Understanding the roles of miRNAs in leukemic cells brings information on a new layer of gene regulation and also provides new markers for improved diagnosis and prognosis, as well as novel therapeutic options for CLL patients. Herein we will focus on the roles of miRNAs in CLL, highlighting what is already known about their function, proposing a novel model of CLL predisposition and progression, and describing the challenges for the near future.

Keywords

CLL miRNAs ZAP-70 IGHV ATM mutation 

Notes

Acknowledgments

Dr. Dana Elena Giza was supported in part by CNCS-UEFISCDI project number 22 from 28/08/2013 (PN-II-ID-PCE-2012-4-0018), and by the Romanian National Research Council (CNCS) Complex Exploratory Research Projects (Grant CEEX 187/2006). Dr. Calin is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in Dr. Calin’s laboratory is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01, The UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI (P50 CA093459), Aim at Melanoma Foundation and the Miriam and Jim Mulva research funds, the Brain SPORE (2P50CA127001), the Center for radiation Oncology Research Project, the Center for Cancer Epigenetics Pilot project, a 2014 Knowledge GAP MDACC grant, a CLL Moonshot pilot project, The UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation, and the Estate of C. G. Johnson, Jr. We would like to give special thanks to Dr. Mircea Ionescu for helping with text for editorial assistance.

References

  1. 1.
    Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell’Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004;101:11755–60.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hallek M. Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment. Am J Hematol. 2013;88:803–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Montserrat E, Rozman C. Chronic lymphocytic leukemia: present status. Ann Oncol. 1995;6:219–35.PubMedGoogle Scholar
  4. 4.
    Bottoni A, Calin GA. MicroRNAs as main players in the pathogenesis of chronic lymphocytic leukemia. Microrna. 2014;2:158–64.CrossRefPubMedGoogle Scholar
  5. 5.
    Ponzoni M, Doglioni C, Caligaris-Cappio F. Chronic lymphocytic leukemia: the pathologist’s view of lymph node microenvironment. Semin Diagn Pathol. 2011;28:161–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Gaidano G, Foa R, Dalla-Favera R. Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest. 2012;122:3432–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hallek M. Signaling the end of chronic lymphocytic leukemia: new frontline treatment strategies. Hematology Am Soc Hematol Educ Program. 2013;2013:138–50.PubMedGoogle Scholar
  8. 8.
    Bullrich F, Fujii H, Calin G, Mabuchi H, Negrini M, Pekarsky Y, Rassenti L, Alder H, Reed JC, Keating MJ, Kipps TJ, Croce CM. Characterization of the 13q14 tumor suppressor locus in CLL: identification of ALT1, an alternative splice variant of the LEU2 gene. Cancer Res. 2001;61:6640–8.PubMedGoogle Scholar
  9. 9.
    Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW, Hamblin TJ, Staudt LM, Oscier DG. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004;363:105–11.CrossRefPubMedGoogle Scholar
  10. 10.
    Chiorazzi N, Allen SL, Ferrarini M. Clinical and laboratory parameters that define clinically relevant B-CLL subgroups. Curr Top Microbiol Immunol. 2005;294:109–33.PubMedGoogle Scholar
  11. 11.
    Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Stilgenbauer S, Bullinger L, Benner A, Wildenberger K, Bentz M, Dohner K, Ho AD, Lichter P, Dohner H. Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia. 1999;13:1331–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Moreno C, Montserrat E. Genetic lesions in chronic lymphocytic leukemia: what’s ready for prime time use? Haematologica. 2010;95:12–5.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia. N Engl J Med. 2000;343:1799–801.CrossRefPubMedGoogle Scholar
  15. 15.
    Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. 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;99:15524–9.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Palamarchuk A, Efanov A, Nazaryan N, Santanam U, Alder H, Rassenti L, Kipps T, Croce CM, Pekarsky Y. 13q14 deletions in CLL involve cooperating tumor suppressors. Blood. 2010;115:3916–22.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med. 2006;12:440–50.CrossRefPubMedGoogle Scholar
  18. 18.
    Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell. 2012;148:1172–87.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Austen B, Powell JE, Alvi A, Edwards I, Hooper L, Starczynski J, Taylor AM, Fegan C, Moss P, Stankovic T. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005;106:3175–82.CrossRefPubMedGoogle Scholar
  20. 20.
    Ambros V. MicroRNAs and developmental timing. Curr Opin Genet Dev. 2011;21:511–7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  22. 22.
    Ambros V, Lee RC, Lavanway A, Williams PT, Jewell D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol. 2003;13:807–18.CrossRefPubMedGoogle Scholar
  23. 23.
    Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci U S A. 2007;104:9667–72.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ, Becker H, Chandler JC, Andino R, Cortes J, Hokland P, Huettner CS, Bhatia R, Roy DC, Liebhaber SA, Caligiuri MA, Marcucci G, Garzon R, Croce CM, Calin GA, Perrotti D. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140:652–65.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A. 2008;105:1608–13.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kim DH, Saetrom P, Snove Jr O, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A. 2008;105:16230–5.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Harfe BD. MicroRNAs in vertebrate development. Curr Opin Genet Dev. 2005;15:410–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Tudor S, Giza DE, Lin HY, Fabris L, Yoshiaki K, D’Abundo L, Toale KM, Shimizu M, Ferracin M, Challagundla KB, Cortez MA, Fuentes-Mattei E, Tulbure D, Gonzalez C, Henderson J, Row M, Rice TW, Ivan C, Negrini M, Fabbri M, Morris JS, Yeung SC, Vasilescu C, Calin GA. Cellular and Kaposi’s sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma. Cell Death Dis. 2014;5, e1559.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Schulte LN, Westermann AJ, Vogel J. Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing. Nucleic Acids Res. 2013;41:542–53.CrossRefPubMedGoogle Scholar
  30. 30.
    Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, Fabbri M, Lerner S, Barron LL, Rassenti LZ, Jiang L, Xiao L, Hu J, Secchiero P, Zauli G, Volinia S, Negrini M, Wierda W, Kipps TJ, Plunkett W, Coombes KR, Abruzzo LV, Keating MJ, Calin GA. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116:945–52.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    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;20:425–37.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, Liu P, Hong M, Miao KR, Liu P, Xu W, Li JY. miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 2012;33:1294–301.CrossRefPubMedGoogle Scholar
  33. 33.
    Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66:11590–3.CrossRefPubMedGoogle Scholar
  34. 34.
    Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–801.CrossRefPubMedGoogle Scholar
  35. 35.
    Calin GA, Croce CM. Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes. Blood. 2009;114:4761–70.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Dohner H, Fischer K, Bentz M, Hansen K, Benner A, Cabot G, Diehl D, Schlenk R, Coy J, Stilgenbauer S, et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995;85:1580–9.PubMedGoogle Scholar
  37. 37.
    Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6:214–30.CrossRefPubMedGoogle Scholar
  38. 38.
    Rao DS, O’Connell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore D. MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1. Immunity. 2010;33:48–59.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fabbri M, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE, Valeri N, Calore F, Sampath D, Fanini F, Vannini I, Musuraca G, Dell’Aquila M, Alder H, Davuluri RV, Rassenti LZ, Negrini M, Nakamura T, Amadori D, Kay NE, Rai KR, Keating MJ, Kipps TJ, Calin GA, Croce CM. Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA. 2011;305:59–67.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Negrini M, Cutrona G, Bassi C, Fabris S, Zagatti B, Colombo M, Ferracin M, D’Abundo L, Saccenti E, Matis S, Lionetti M, Agnelli L, Gentile M, Recchia AG, Bossio S, Reverberi D, Rigolin G, Calin GA, Sabbioni S, Russo G, Tassone P, Morabito F, Ferrarini M, Neri A. microRNAome expression in chronic lymphocytic leukemia: comparison with normal B-cell subsets and correlations with prognostic and clinical parameters. Clin Cancer Res. 2014;20:4141–53.CrossRefPubMedGoogle Scholar
  41. 41.
    Cui B, Chen L, Zhang S, Mraz M, Fecteau JF, Yu J, Ghia EM, Zhang L, Bao L, Rassenti LZ, Messer K, Calin GA, Croce CM, Kipps TJ. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia. Blood. 2014;124:546–54.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ferrajoli A, Shanafelt TD, Ivan C, Shimizu M, Rabe KG, Nouraee N, Ikuo M, Ghosh AK, Lerner S, Rassenti LZ, Xiao L, Hu J, Reuben JM, Calin S, You MJ, Manning JT, Wierda WG, Estrov Z, O’Brien S, Kipps TJ, Keating MJ, Kay NE, Calin GA. Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 2013;122:1891–9.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8:467–77.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang HG, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood. 1998;91:3379–89.PubMedGoogle Scholar
  45. 45.
    Tsujimoto Y, Louie E, Bashir MM, Croce CM. The reciprocal partners of both the t(14; 18) and the t(11; 14) translocations involved in B-cell neoplasms are rearranged by the same mechanism. Oncogene. 1988;2:347–51.PubMedGoogle Scholar
  46. 46.
    Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008;105:5166–71.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sampath D, Calin GA, Puduvalli VK, Gopisetty G, Taccioli C, Liu CG, Ewald B, Liu C, Keating MJ, Plunkett W. Specific activation of microRNA106b enables the p73 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation. Blood. 2009;113:3744–53.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol. 2008;18:505–16.CrossRefPubMedGoogle Scholar
  50. 50.
    Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T. Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther. 2010;17:398–408.CrossRefPubMedGoogle Scholar
  51. 51.
    Ghosh AK, Shanafelt TD, Cimmino A, Taccioli C, Volinia S, Liu CG, Calin GA, Croce CM, Chan DA, Giaccia AJ, Secreto C, Wellik LE, Lee YK, Mukhopadhyay D, Kay NE. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood. 2009;113:5568–74.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, Ambesi-Impiombato A, Califano A, Migliazza A, Bhagat G, Dalla-Favera R. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell. 2010;17:28–40.CrossRefPubMedGoogle Scholar
  53. 53.
    Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K, Toro JR, Zenger VE, Metcalf RA, Marti GE. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood. 2007;109:5079–86.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Haiat S, Billard C, Quiney C, Ajchenbaum-Cymbalista F, Kolb JP. Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia. Immunology. 2006;118:281–92.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Balatti V, Pekarky Y, Rizzotto L, Croce CM. miR deregulation in CLL. Adv Exp Med Biol. 2013;792:309–25.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zapata JM, Krajewska M, Morse 3rd HC, Choi Y, Reed JC. 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;101:16600–5.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Santanam U, Zanesi N, Efanov A, Costinean S, Palamarchuk A, Hagan JP, Volinia S, Alder H, Rassenti L, Kipps T, Croce CM, Pekarsky Y. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A. 2010;107:12210–5.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux L. microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood. 2009;113:5237–45.CrossRefPubMedGoogle Scholar
  59. 59.
    Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104:15805–10.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840–7.PubMedGoogle Scholar
  61. 61.
    Kikushige Y, Ishikawa F, Miyamoto T, Shima T, Urata S, Yoshimoto G, Mori Y, Iino T, Yamauchi T, Eto T, Niiro H, Iwasaki H, Takenaka K, Akashi K. Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell. 2011;20:246–59.CrossRefPubMedGoogle Scholar
  62. 62.
    Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ. miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1. Blood. 2014;124:84–95.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ferracin M, Zagatti B, Rizzotto L, Cavazzini F, Veronese A, Ciccone M, Saccenti E, Lupini L, Grilli A, De Angeli C, Negrini M, Cuneo A. MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Mol Cancer. 2010;9:123.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Zenz T, Mohr J, Eldering E, Kater AP, Buhler A, Kienle D, Winkler D, Durig J, van Oers MH, Mertens D, Dohner H, Stilgenbauer S. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009;113:3801–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Calin GA, Croce CM. Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol. 2006;33:167–73.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Experimental Therapeutics DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of HematologyFundeni Clinical InstituteBucharestRomania
  3. 3.The RNA Interference and Non-coding RNA Center, MD Anderson Cancer Center, Texas State UniversityHoustonUSA

Personalised recommendations