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Cell free nucleic acids as diagnostic and prognostic marker in leukemia

  • Maryam Eini
  • Seyed Ali Nojoumi
  • Mohammad-Amin Saki
  • Abbas Khosravi
review
  • 99 Downloads

Summary

Nucleic acids in circulation, called cell free DNA (cfDNA) and cell free RNA (cfRNA), have recently been analyzed as suitable diagnostic and prognostic markers in cancer. There have also been several reports about the role of this type of marker in leukemia. The relevant literature was identified by a PubMed search (2000–2017) of English-language literature using the terms “cell free DNA”, “Leukemia” and Micro-RNA. Many quantitative and qualitative cfDNA biomarkers including copy number alteration, mutation, LOH and micro-RNA deregulated expression have been investigated in different studies, indicating promising results to distinguish patients from healthy individuals. The findings of this study indicate that nucleic acids in circulation have a high diagnostic and prognostic value in leukemic patients and, thus, have the potential to be used alongside the usual methods in the management of this disease.

Keywords

Nucleic acids Leukemia Diagnosis Prognosis 

Notes

Acknowledgements

We wish to thank all our colleagues in Golestan Hospital’s Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences.

Compliance with ethical guidelines

Conflict of interest

M. Eini, S.A. Nojoumi, M.-A. Saki, and A. Khosravi declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Mandel P, Metais P. Les acides nucleiques du plasma sanguin chez l’homme. C R Seances Soc Biol Fil. 1948;142:241–3.PubMedGoogle Scholar
  2. 2.
    Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao S‑L. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev. 1994;3(1):67–71.PubMedGoogle Scholar
  3. 3.
    Tug S, Helmig S, Menke J, Zahn D, Kubiak T, Schwarting A, et al. Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients. Cell Immunol. 2014;292(1):32–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Jing R, Cui M, Wang H, Ju S. Cell-free DNA: characteristics, detection and its applications in myocardial infarction. Curr Pharm Des. 2013;19(28):5135–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Gielis E, Ledeganck K, De Winter B, Del Favero J, Bosmans JL, Claas F, et al. Cell-free DNA: an upcoming biomarker in transplantation. Am J Transplant. 2015;15(10):2541–51.CrossRefPubMedGoogle Scholar
  6. 6.
    Lun FM, Tsui NB, Chan KA, Leung TY, Lau TK, Charoenkwan P, et al. Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. Proc Natl Acad Sci. 2008;105(50):19920–5.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fan HC, Gu W, Wang J, Blumenfeld YJ, El-Sayed YY, Quake SR. Non-invasive prenatal measurement of the fetal genome. Nature. 2012;487(7407):320–4.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.CrossRefPubMedGoogle Scholar
  9. 9.
    Huang YK, Yu JC. Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis: an update and review. World J Gastroenterol. 2015;21(34):9863–86.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Benesova L, Belsanova B, Suchanek S, Kopeckova M, Minarikova P, Lipska L, et al. Mutation-based detection and monitoring of cell-free tumor DNA in peripheral blood of cancer patients. Anal Biochem. 2013;433(2):227–34.CrossRefPubMedGoogle Scholar
  11. 11.
    Kuo YB, Chen JS, Fan CW, Li YS, Chan EC. Comparison of KRAS mutation analysis of primary tumors and matched circulating cell-free DNA in plasmas of patients with colorectal cancer. Clin Chim Acta. 2014;433:284–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Chimonidou M, Tzitzira A, Strati A, Sotiropoulou G, Sfikas C, Malamos N, et al. CST6 promoter methylation in circulating cell-free DNA of breast cancer patients. Clin Biochem. 2013;46(3):235–40.CrossRefPubMedGoogle Scholar
  13. 13.
    Sun FK, Fan YC, Zhao J, Zhang F, Gao S, Zhao ZH, et al. Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients. Dig Dis Sci. 2013;58(4):1010–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Nygaard AD, Garm Spindler KL, Pallisgaard N, Andersen RF, Jakobsen A. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer. Lung Cancer. 2013;79(3):312–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem. 2015;61(1):112–23.CrossRefPubMedGoogle Scholar
  16. 16.
    Lasorella A, Sanson M, Iavarone A. FGFR-TACC gene fusions in human glioma. Neuro-oncology. 2016;19(4):475.  https://doi.org/10.1093/neuonc/now240.Google Scholar
  17. 17.
    Zoratto F, Rossi L, Verrico M, Papa A, Basso E, Zullo A, et al. Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis. Tumour Biol. 2014;35(7):6195–206.CrossRefPubMedGoogle Scholar
  18. 18.
    Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, et al. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med. 2012;4(162):162ra54.CrossRefGoogle Scholar
  19. 19.
    Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–12.CrossRefPubMedGoogle Scholar
  20. 20.
    Ulivi P, Silvestrini R. Role of quantitative and qualitative characteristics of free circulating DNA in the management of patients with non-small cell lung cancer. Cell Oncol. 2013;36(6):439–48.CrossRefGoogle Scholar
  21. 21.
    Yin C, Luo C, Hu W, Ding X, Yuan C, Wang F. Quantitative and qualitative analysis of circulating cell-free DNA can be used as an adjuvant tool for prostate cancer screening: a meta-analysis. Dis Markers. 2016;  https://doi.org/10.1155/2016/3825819.Google Scholar
  22. 22.
    Francis G, Stein S. Circulating cell-free tumour DNA in the management of cancer. Int J Mol Sci. 2015;16(6):14122–42.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Esposito A, Bardelli A, Criscitiello C, Colombo N, Gelao L, Fumagalli L, et al. Monitoring tumor-derived cell-free DNA in patients with solid tumors: clinical perspectives and research opportunities. Cancer Treat Rev. 2014;40(5):648–55.CrossRefPubMedGoogle Scholar
  24. 24.
    Jiang Y, Pan SY, Xia WY, Chen D, Wang H, Zhang LX, et al. Dynamic monitoring of plasma circulating DNA in patients with acute myeloid leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20(1):53–6.PubMedGoogle Scholar
  25. 25.
    Gao YJ, He YJ, Yang ZL, Shao HY, Zuo Y, Bai Y, et al. Increased integrity of circulating cell-free DNA in plasma of patients with acute leukemia. Clin Chem Lab Med. 2010;48(11):1651–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Quan J, Gao YJ, Yang ZL, Chen H, Xian JR, Zhang SS, et al. Quantitative detection of circulating nucleophosmin mutations DNA in the plasma of patients with acute myeloid leukemia. Int J Med Sci. 2015;12(1):17–22.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhong L, Meng WT, Zheng Q, Zhou J, Jia YQ. FLT3-ITD detection of free DNA in plasma from 235 patients with acute myeloid leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17(5):1144–8.PubMedGoogle Scholar
  28. 28.
    Ma W, Kantarjian H, Zhang X, Jilani I, Sheikholeslami MR, Donahue AC, et al. Detection of nucleophosmin gene mutations in plasma from patients with acute myeloid leukemia: clinical significance and implications. Cancer Biomark. 2009;5(1):51–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Jilani I, Estey E, Manshuri T, Caligiuri M, Keating M, Giles F, et al. Better detection of FLT3 internal tandem duplication using peripheral blood plasma DNA. Leukemia. 2003;17(1):114–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N‑ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86(4):774–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Rogers A, Joe Y, Manshouri T, Dey A, Jilani I, Giles F, et al. Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia. Blood. 2004;103(7):2799–801.CrossRefPubMedGoogle Scholar
  32. 32.
    Fayyad-Kazan H, Bitar N, Najar M, Lewalle P, Fayyad-Kazan M, Badran R, et al. Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia. J Transl Med. 2013;11(3579719):31.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ohyashiki JH, Umezu T, Kobayashi C, Hamamura RS, Tanaka M, Kuroda M, et al. Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in vivo assessment of cell to plasma ratio of miR-92a. BMC Res Notes. 2010;3:347.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLOS ONE. 2009;4(5):e5532.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cheng SH, Lau KM, Li CK, Chan NP, Ip RK, Cheng CK, et al. Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction. PLOS ONE. 2013;8(7):e69467.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Schwarz AK, Stanulla M, Cario G, Flohr T, Sutton R, Moricke A, et al. Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. Ann Hematol. 2009;88(9):897–905.CrossRefPubMedGoogle Scholar
  37. 37.
    Lu XJ, Jiang Q, Huang PL, Li G, Zhang WJ, Zhao XX, et al. Preliminary analysis of aberrant expression of plasma miR-223 in pediatric acute lymphoblastic leukemia with a direct RT-PCR assay. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21(1):68–72.PubMedGoogle Scholar
  38. 38.
    Fawzy A, Sweify KM, El-Fayoumy HM, Nofal N. Quantitative analysis of plasma cell-free DNA and its DNA integrity in patients with metastatic prostate cancer using ALU sequence. J Egypt Natl Canc Inst. 2016;28(4):235.  https://doi.org/10.1016/j.jnci.2016.08.003.CrossRefPubMedGoogle Scholar
  39. 39.
    Qin Z, Ljubimov VA, Zhou C, Tong Y, Liang J. Cell-free circulating tumor DNA in cancer. Chin J Cancer. 2016;35:36.  https://doi.org/10.1186/s40880-016-0092-4.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hardikar AA, Farr RJ, Joglekar MV. Circulating microRNAs: understanding the limits for quantitative measurement by real-time PCR. J Am Heart Assoc. 2014;3(1):e792.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Francis G, Stein S. Circulating cell-free tumour DNA in the management of cancer. Int J Mol Sci. 2015;16(6):14122–42.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zimmermann BG, Grill S, Holzgreve W, Zhong XY, Jackson LG, Hahn S. Digital PCR: a powerful new tool for noninvasive prenatal diagnosis? Prenat Diagn. 2008;28(12):1087–93.CrossRefPubMedGoogle Scholar
  44. 44.
    Lauring J, Park BH. BEAMing sheds light on drug resistance. Clin Cancer Res. 2011;17(24):7508–10.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, et al. BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles. Mol Ther Nucleic Acids. 2013;2:e109.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Marzese DM, Hirose H, Hoon DS. Diagnostic and prognostic value of circulating tumor-related DNA in cancer patients. Expert Rev Mol Diagn. 2013;13(8):827–44.CrossRefPubMedGoogle Scholar
  47. 47.
    Mantadakis E, Katzilakis N, Foundoulaki E, Kalmanti M. Moderate intravenous sedation with fentanyl and midazolam for invasive procedures in children with acute lymphoblastic leukemia. J Pediatr Oncol Nurs. 2009;26(4):217–22.CrossRefPubMedGoogle Scholar
  48. 48.
    Salari F, Shahjahani M, Shahrabi S, Saki N. Minimal residual disease in acute lymphoblastic leukemia: optimal methods and clinical relevance, pitfalls and recent approaches. Med Oncol. 2014;31(11):266.CrossRefPubMedGoogle Scholar
  49. 49.
    Warton K, Samimi G. Methylation of cell-free circulating DNA in the diagnosis of cancer. Front Mol Biosci. 2015;2:13.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Maryam Eini
    • 1
  • Seyed Ali Nojoumi
    • 2
  • Mohammad-Amin Saki
    • 3
  • Abbas Khosravi
    • 4
  1. 1.Immunology Research CenterIran University of Medical SciencesTehranIran
  2. 2.Microbiology Research CenterPasteur Institute of IranTehranIran
  3. 3.Sana Institute of Higher EducationSariIran
  4. 4.Hematopoietic Stem Cell Research CenterShahid Beheshti University of Medical SciencesTehranIran

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