Clinical Value of miR-3151 Overexpression in Synergistic Interaction with BAALC Host Gene in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

AI Shakirova, IM Barkhatov, AI Churkina, NN Mamaev, LS Zubarovskaya, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alena Igorevna Shakirova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail:

For citation: Shakirova AI, Barkhatov IM, Churkina AI, et al. Clinical Value of miR-3151 Overexpression in Synergistic Interaction with BAALC Host Gene in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2019;12(3):303–8 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-303-308


Background. Among a multitude of molecular genetic changes underlying acute myeloid leukemia (AML) disordered epigenetic regulation is of special importance. It includes expression change in miR-3151 gene forming a part of BAALC gene on chromosome 8 in q22.3 locus. At present BAALC gene overexpression is observed in a half of AML patients. A considerable part of them shows a combination of it with an increased transcriptional activity of miR-3151 gene, which is associated with the poorest AML prognosis.

Aim. To assess the prognostic value of miR-3151 overexpression in synergistic interaction with BAALC host gene in AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. The trial included bone marrow samples taken from 10 healthy SCT donors and 29 AML patients after receiving allo-HSCT. Relative miR-3151 expression level and relative BAALC copy number were measured by quantitative real-time polymerase chain reaction.

Results. The analysis yielded a poor correlation between miR-3151 expression level and blast cell count in bone marrow (r = 0.330; = 0.005) as well as between the expression levels of miR-3151 and BAALC (r = 0.273; = 0.020). In addition, a great prognostic value of miR-315 overexpression in post-transplantation period was confirmed (= 0.005). Patients with miR-315 and BAALC co-expression in post-transplantation period have also the poorest prognosis than the control group with regard to both disease-free survival and relapse risks within 2 years after allo-HSCT.

Conclusion. Monitoring expression level of miR-3151 and its host gene BAALC in AML patients after receiving allo-HSCT seems to be important not only in AML prognosis but also in therapy efficacy evaluation.

Keywords: acute myeloid leukemia, miR-3151, BAALC, prognosis, allogeneic hematopoietic stem cell transplantation.

Received: October 22, 2018

Accepted: June 7, 2019

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  1. Testa U, Pelosi E. MicroRNAs expressed in hematopoietic stem/progenitor cells are deregulated in acute myeloid leukemias. Leuk Lymphoma. 2015;56(5):1466–74. doi: 3109/10428194.2014.955019.

  2. Liao Q, Wang B, Li X, Jiang G. miRNAs in acute myeloid leukemia. Oncotarget. 2017;8(2):3666–82. doi: 10.18632/oncotarget.12343.

  3. Ambros V. MicroRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6. doi: 1016/S0092-8674(01)00616-X.

  4. Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol. 2011;29(5):475–86. doi: 10.1200/JCO.2010.30.2554.

  5. Ehtesham N, Sharifi M. From conventional therapy toward microRNA-based therapy in acute promyelocytic leukemia. Adv Biomed Res. 2016;5:187. doi: 10.4103/2277-9175.190996.

  6. Li Z, Lu J, Sun M, et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci. 2008;105:15535–40. doi: 10.1073/pnas.0808266105.

  7. Dixon-McIver A, East P, Mein CA, et al. Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One. 2008;3(5):е2141. doi: 10.1371/journal.pone.0002141.

  8. Jongen-Lavrencic M, Sun SM, Dijkstra MK, et al. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood. 2008;111(10):5078–85. doi: 10.1182/blood-2008-01-133355.

  9. Stark M, Tyagi S, Nancarrow D, et al. Characterization of the Melanoma miRNAome by Deep Sequencing. PLoS One. 2010;5(3):e9685. doi: 10.1371/journal.pone.0009685.

  10. Eisfeld A-K, Schwind S, Patel R, et al. Intronic miR-3151 within BAALC drives leukemogenesis by deregulating the TP53 Pathway. Sci Signal. 2014;7(321):ra36. doi: 10.1126/scisignal.2004762.

  11. Eisfeld A-K, Marcucci G, Maharry K, et al. miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia. Blood. 2012;120(2):249–58. doi: 10.1182/blood-2012-02-408492.

  12. Diaz-Beya M, Brunet S, Nomdedeu J, et al. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia. Blood Cancer J. 2015;5(10):e352. doi: 10.1038/bcj.2015.76.

  13. Weber S, Haferlach T, Alpermann T, et al. Feasibility of BAALC gene expression for detection of minimal residual disease and risk stratification in normal karyotype acute myeloid leukaemia. Br J Haematol. 2016;175(5):904–16. doi: 10.1111/bjh.14343.

  14. Shakirova A, Barkhatov I, Churkina A, et al. Prognostic significance of BAALC overexpression in patients with AML during the posttransplant period. Cellular Therapy and Transplantation. 2018;7(2):54–63. doi: 10.18620/ctt-1866-8836-2018-7-2–54-63.

  15. Schnerch D, Yalcintepe J, Schmidts A, et al. Cell cycle control in acute myeloid leukemia. Am J Cancer Res. 2012;2(5):508–28.

  16. Cilloni D, Renneville A, Hermitte F, et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study. J Clin Oncol. 2009;27(31):5195–201. doi: 10.1200/JCO.2009.22.4865.

  17. Мамаев Н.Н., Горбунова А.В., Бархатов И.М. и др. Молекулярный мониторинг течения острых миелоидных лейкозов по уровню экспрессии гена WT1 после аллогенной трансплантации гемопоэтических стволовых клеток. Клиническая онкогематология. 2015;8(3):309–20. doi: 10.21320/2500-2139-2015-8-3-309-320.

    [Mamaev NN, Gorbunova AV, Barkhatov IM, et al. Molecular Monitoring of WT1 Gene Expression Level in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2015;8(3):309–20. doi: 21320/2500-2139-2015-8-3-309-320. (In Russ)]

  18. Hosen N, Sonoda Y, Oji Y, et al. Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol. 2002;116(2):409–20. doi: 10.1046/j.1365-2141.2002.03261.x.

  19. Ellisen LW, Carlesso N, Cheng T, et al. The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J. 2001;20(8):1897–909. doi: 10.1093/emboj/20.8.1897.

  20. Panyajai P, Amnajphook N, Keawsangthongcharoen S, et al. Study of Leukemic Stem Cell Population (CD34+/CD38-) and WT1 Protein Expression in Human Leukemic Cell Lines. J Assoc Med Sci. 2018;51(1):38–44. doi: 10.14456/jams.2018.5.

  21. Baldus C, Tanner S, Kusewitt D, et al. BAALC, a novel marker of human hematopoietic progenitor cells. Exp Hematol. 2003;31(11):1051–6. doi: 10.1016/j.exphem.2003.08.004.

  22. Najima Y, Ohashi K, Kawamura M, et al. Molecular monitoring of BAALC expression in patients with CD34-positive acute leukemia. Int J Hematol. 2010;91(4):636–45. doi: 10.1007/s12185-010-0550-8.

  23. Xiao S, Shen JZ, Huang JL, et al. Prognostic significance of the BAALC gene expression in adult patients with acute myeloid leukemia: A meta-analysis. Mol Clin Oncol. 2015;3(4):880–8. doi: 10.3892/mco.2015.562.

  24. Lucena-Araujo A, Pereira-Martins D, Koury L, et al. Clinical impact of BAALC expression in high-risk acute promyelocytic leukemia. Blood Adv. 2017;1(21):1807–14. doi: 10.1182/bloodadvances.2017005926.