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Article

Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia

  • Authors:
    • Ewa Musialik
    • Mateusz Bujko
    • Paulina Kober
    • Monika Anna Grygorowicz
    • Marta Libura
    • Marta Przestrzelska
    • Przemysław Juszczyński
    • Katarzyna Borg
    • Izabela Florek
    • Małgorzata Jakóbczyk
    • Janusz Aleksander Siedlecki
  • View Affiliations / Copyright

    Affiliations: Department of Molecular and Translational Oncology, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02‑781, Poland, Department of Immunology, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02‑781, Poland, Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Warsaw 02‑097, Poland, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, Warsaw 02‑109, Poland, Department of Hematology, Jagiellonian University, Cracow 31‑501, Poland
  • Pages: 3948-3954
    |
    Published online on: January 13, 2015
       https://doi.org/10.3892/mmr.2015.3196
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Abstract

HOXA genes encode transcription factors, which are crucial for embryogenesis and tissue differentiation and are involved in the early stages of hematopoiesis. Aberrations in HOXA genes and their cofactor MEIS1 are found in human neoplasms, including acute myeloid leukemia (AML). The present study investigated the role of HOXA4, HOXA5 and MEIS1 promoter DNA methylation and mRNA expression in AML. Samples from 78 AML patients and 12 normal bone marrow (BM) samples were included. The levels of promoter DNA methylation were determined using quantitative methylation‑specific polymerase chain reaction (PCR; qMSP) and the relative expression levels were measured using reverse transcription quantitative PCR in Ficoll‑separated BM mononuclear cells and in fluorescent activated cell sorting‑sorted populations of normal hematopoietic progenitors. In total, 38.1 and 28.9% of the patients exhibited high methylation levels of HOXA4 and HOXA5, respectively, compared with the control samples, and MEIS1 methylation was almost absent. An inverse correlation between HOXA4 methylation and expression was identified in a group of patients with a normal karyotype (NK AML). An association between the genes was observed and correlation between the DNA methylation and expression levels of the HOXA gene promoter with the expression of MEIS1 was observed. Patients with favorable chromosomal aberrations revealed a low level of HOXA4 methylation and decreased expression levels of HOXA5 and MEIS1 compared with the NK AML and the adverse cytogenetic risk patients. The NK AML patients with NPM1 mutations exhibited elevated HOXA4 methylation and expression levels of HOXA5 and MEIS1 compared with the NPM1 wild‑type patients. Comparison of the undifferentiated BM‑derived hematopoietic CD34+CD38low, CD34+CD38+ and CD15+ cells revealed a gradual decrease in the expression levels of these three genes and an increase in HOXA4 promoter methylation. This differentiation‑associated variability was not observed in AML, which was classified according to the French‑American‑British system.
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Copy and paste a formatted citation
Spandidos Publications style
Musialik E, Bujko M, Kober P, Grygorowicz MA, Libura M, Przestrzelska M, Juszczyński P, Borg K, Florek I, Jakóbczyk M, Jakóbczyk M, et al: Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia. Mol Med Rep 11: 3948-3954, 2015.
APA
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M.A., Libura, M., Przestrzelska, M. ... Siedlecki, J.A. (2015). Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia. Molecular Medicine Reports, 11, 3948-3954. https://doi.org/10.3892/mmr.2015.3196
MLA
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M. A., Libura, M., Przestrzelska, M., Juszczyński, P., Borg, K., Florek, I., Jakóbczyk, M., Siedlecki, J. A."Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia". Molecular Medicine Reports 11.5 (2015): 3948-3954.
Chicago
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M. A., Libura, M., Przestrzelska, M., Juszczyński, P., Borg, K., Florek, I., Jakóbczyk, M., Siedlecki, J. A."Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia". Molecular Medicine Reports 11, no. 5 (2015): 3948-3954. https://doi.org/10.3892/mmr.2015.3196
Copy and paste a formatted citation
x
Spandidos Publications style
Musialik E, Bujko M, Kober P, Grygorowicz MA, Libura M, Przestrzelska M, Juszczyński P, Borg K, Florek I, Jakóbczyk M, Jakóbczyk M, et al: Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia. Mol Med Rep 11: 3948-3954, 2015.
APA
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M.A., Libura, M., Przestrzelska, M. ... Siedlecki, J.A. (2015). Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia. Molecular Medicine Reports, 11, 3948-3954. https://doi.org/10.3892/mmr.2015.3196
MLA
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M. A., Libura, M., Przestrzelska, M., Juszczyński, P., Borg, K., Florek, I., Jakóbczyk, M., Siedlecki, J. A."Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia". Molecular Medicine Reports 11.5 (2015): 3948-3954.
Chicago
Musialik, E., Bujko, M., Kober, P., Grygorowicz, M. A., Libura, M., Przestrzelska, M., Juszczyński, P., Borg, K., Florek, I., Jakóbczyk, M., Siedlecki, J. A."Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia". Molecular Medicine Reports 11, no. 5 (2015): 3948-3954. https://doi.org/10.3892/mmr.2015.3196
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