Aberrant Expression of the miR-181b/miR-222 after Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia

  • Mahdiyar Iravani Saadi
  • Nargess Arandi
  • Ramin Yaghobi
  • Negar Azarpira
  • Bita Geramizadeh
  • Mani RamziEmail author
Original Article


Recently, dysregulated expression of various micro RNAs has been reported in hematologic malignancies, especially AML disease which affects normal hematopoiesis in these patients and thereby contribute to clinical outcome of AML patients, associated with either poor or favorable prognosis. Herein, we evaluated the expression of miR-181b and miR-222 in acute myeloid leukemia patients and correlation with response to therapy after hematopoietic stem cell transplantation. Eighty newly diagnosed AML patients and 80 healthy controls were recruited. The expression of miR-181b and miR-222 was evaluated by real-time SYBR Green PCR method. miR-181b gene expression was significantly increased (4.7 fold) whereas miR-222 was decreased (18.3 fold) in AML patients compared to controls (P = 0.03 and P < 0.001, respectively). Both miR-181b and miR-222 were not associated with response to treatment (P > 0.05). Also, miR-181b and miR-222 were not differentially expressed in AML patients with M3 compared to non-M3 FAB subtypes (P > 0.05). miR-181b and miR-222 are aberrantly expressed in AML patients and their baseline level is not associated with response to treatment.


Acute myeloid leukemia (AML) miR-181b miR-222 Chemosensitivity 



The authors would like to thanks, Dr. Nasrin Shokrpour at Center for Development of Clinical Research of Namazi Hospital for editorial assistance.


This study was financially supported by Shiraz University of Medical Sciences [Grant Number 94-01-104-11279].

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373(9674):1550–1561CrossRefGoogle Scholar
  2. 2.
    Marcucci G, Mrozek K, Radmacher MD, Garzon R, Bloomfield CD (2011) The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood 117(4):1121–1129CrossRefGoogle Scholar
  3. 3.
    Shivarov V, Bullinger L (2014) Expression profiling of leukemia patients: key lessons and future directions. Exp Hematol 42(8):651–660CrossRefGoogle Scholar
  4. 4.
    Khalaj M, Tavakkoli M, Stranahan AW, Park CY (2014) Pathogenic microRNA’s in myeloid malignancies. Front Genet 5:361CrossRefGoogle Scholar
  5. 5.
    Yeh C-H, Moles R, Nicot C (2016) Clinical significance of microRNAs in chronic and acute human leukemia. Mol Cancer 15(1):37CrossRefGoogle Scholar
  6. 6.
    Rommer A, Steinleitner K, Hackl H, Schneckenleithner C, Engelmann M, Scheideler M, Vlatkovic I, Kralovics R, Cerny-Reiterer S, Valent P (2013) Overexpression of primary microRNA 221/222 in acute myeloid leukemia. BMC Cancer 13(1):364CrossRefGoogle Scholar
  7. 7.
    Brioschi M, Fischer J, Cairoli R, Rossetti S, Pezzetti L, Nichelatti M, Turrini M, Corlazzoli F, Scarpati B, Morra E (2010) Down-regulation of microRNAs 222/221 in acute myelogenous leukemia with deranged core-binding factor subunits. Neoplasia 12(11):866IN862–876IN863CrossRefGoogle Scholar
  8. 8.
    Schwind S, Maharry K, Radmacher MD, Mrózek K, Holland KB, Margeson D, Whitman SP, Hickey C, Becker H, Metzeler KH (2010) 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(36):5257–5264CrossRefGoogle Scholar
  9. 9.
    Weng H, Lal K, Yang FF, Chen J (2015) The pathological role and prognostic impact of miR-181 in acute myeloid leukemia. Cancer Genet 208(5):225–229CrossRefGoogle Scholar
  10. 10.
    Crossland RE, Norden J, Juric MK, Green K, Pearce KF, Lendrem C, Greinix HT, Dickinson AM (2017) Expression of serum micrornas is altered during acute graft-versus-host disease. Front Immunol 8:308Google Scholar
  11. 11.
    Tomuleasa C, Fuji S, Cucuianu A, Kapp M, Pileczki V, Petrushev B, Selicean S, Tanase A, Dima D, Berindan-Neagoe I (2015) MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation. Ann Hematol 94(7):1081–1092CrossRefGoogle Scholar
  12. 12.
    Xiao B, Wang Y, Li W, Baker M, Guo J, Corbet K, Tsalik EL, Li Q-J, Palmer SM, Woods CW (2013) Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease. Blood 122(19):3365–3375CrossRefGoogle Scholar
  13. 13.
    Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18(4):295–304CrossRefGoogle Scholar
  14. 14.
    Mitelman F (1995) ISCN 1995: an international system for human cytogenetic nomenclature (1995): recommendations of the International Standing Committee on Human Cytogenetic Nomenclature, Memphis, Tennessee, USA, 9–13 Oct 1994. Karger Medical and Scientific PublishersGoogle Scholar
  15. 15.
    Chen C-Z, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654):83–86CrossRefGoogle Scholar
  16. 16.
    Li X, Zhang J, Gao L, McClellan S, Finan M, Butler T, Owen L, Piazza G, Xi Y (2012) MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit. Cell Death Differ 19(3):378–386CrossRefGoogle Scholar
  17. 17.
    Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Perez-Ordonez B, Gilbert R (2009) Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet 18(24):4818–4829CrossRefGoogle Scholar
  18. 18.
    Chen H, Chen Q, Fang M, Mi Y (2010) microRNA-181b targets MLK2 in HL-60 cells. Sci China Life Sci 53(1):101–106CrossRefGoogle Scholar
  19. 19.
    le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafrè SA (2007) Regulation of the p27Kip1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26(15):3699–3708CrossRefGoogle Scholar
  20. 20.
    Marcucci G, Radmacher MD, Mrózek K, Bloomfield CD (2009) MicroRNA expression in acute myeloid leukemia. Curr Hematol Malig Rep 4(2):83–88CrossRefGoogle Scholar
  21. 21.
    Isken F, Steffen B, Merk S, Dugas M, Markus B, Tidow N, Zühlsdorf M, Illmer T, Thiede C, Berdel WE (2008) Identification of acute myeloid leukaemia associated microRNA expression patterns. Br J Haematol 140(2):153–161CrossRefGoogle Scholar
  22. 22.
    Gimondi S, Dugo M, Vendramin A, Bermema A, Biancon G, Cavané A, Corradini P, Carniti C (2016) Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation. Exp Hematol 44(7):624–634.e621CrossRefGoogle Scholar
  23. 23.
    Li H, Yang BB (2013) Friend or foe: the role of microRNA in chemotherapy resistance. Acta Pharmacol Sin 34(7):870–879CrossRefGoogle Scholar
  24. 24.
    Butrym A, Rybka J, Baczyńska D, Poręba R, Mazur G, Kuliczkowski K (2016) Expression of microRNA-181 determines response to treatment with azacitidine and predicts survival in elderly patients with acute myeloid leukaemia. Oncol Lett 12(4):2296–2300CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  1. 1.Hematology Research CenterShiraz University of Medical SciencesShirazIran
  2. 2.Shiraz Transplant Research CenterShiraz University of Medical SciencesShirazIran

Personalised recommendations