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Mirzaei A, Mohammadi S, Ghaffari SH, et al. Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia. Asian Pac J Cancer Prev. 2017;18(6):1707-1715doi: 10.22034/APJCP.2017.18.6.1707.
Mirzaei, A., Mohammadi, S., Ghaffari, S. H., Nikbakht, M., Bashash, D., Alimoghaddam, K., & Ghavamzadeh, A. (2017). Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia. Asian Pacific journal of cancer prevention : APJCP, 18(6), 1707-1715. https://doi.org/10.22034/APJCP.2017.18.6.1707
Mirzaei, Akram, et al. "Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia." Asian Pacific journal of cancer prevention : APJCP vol. 18,6 (2017): 1707-1715. doi: https://doi.org/10.22034/APJCP.2017.18.6.1707
Mirzaei A, Mohammadi S, Ghaffari SH, Nikbakht M, Bashash D, Alimoghaddam K, Ghavamzadeh A. Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia. Asian Pac J Cancer Prev. 2017 Jun 25;18(6):1707-1715. doi: 10.22034/APJCP.2017.18.6.1707. PMID: 28670893; PMCID: PMC6373801.
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Asian Pac J Cancer Prev. 2017 Jun 25;18(6):1707-1715. doi: 10.22034/APJCP.2017.18.6.1707.

Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia.

Asian Pacific journal of cancer prevention : APJCP

Akram Mirzaei, Saeed Mohammadi, Seyed H Ghaffari, Mohsen Nikbakht, Davood Bashash, Kamran Alimoghaddam, Ardeshir Ghavamzadeh

Affiliations

  1. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. Email:[email protected], [email protected]

PMID: 28670893 PMCID: PMC6373801 DOI: 10.22034/APJCP.2017.18.6.1707

Abstract

Despite impressive advances in therapeutic approaches, long-term survival with acute myeloid leukemia (AML) is low as a result of treatment resistance and frequent relapse. Among multitude oncogenic proteins involved in acquisition of a chemo-resistanr phenotype, osteopontin (OPN) recently has attracted marked attention. In spite of the well-defined association between OPN expression and cure rate with solid tumors, there is a scarcity of information on any role of this protein in AML cases. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that isoform expression levels may impact on regulation of apoptosis in AML cells in response to conventional chemotherapeutic drugs and its relation to relapse. To investigate associations between induction of apoptosis and OPN isoform expression, two distinct AML cell lines (KG-1 as a leukemic stem cell model and U937) were treated with chemotherapy drugs, and cell viability and apoptosis were evaluated by MTT and Annexin/PI assay. After determination of appropriate drug doses, mRNA expression levels of OPN isoforms and OPN-related genes were investigated. Our results demonstrated for the first time that acquired up-regulation of OPN-b and c isoforms might prevent conventional chemotherapy regimen-induced apoptosis in AML cells. Moreover, upregulation of OPN-b and c in AML cells appears concurrent with upregulation of AKT/VEGF/CXCR4/STAT3/ IL-6 gene expression. To sum up, this study suggests that OPN-b and c isoforms could be considered as unique beneficial molecular biomarkers associated with leukemic stem cell chemoresistance. Hence, they have potential as molecular candidates for detection of minimal residual disease (MRD) and determination of remission in AML patients. Further evaluation with quantative real time PCR on patient samples for confirmation appears warranted.

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Keywords: Osteopontin; leukemis stem cells; chemoresistance; acute myeloid leukemia

References

  1. Nat Med. 2000 Dec;6(12):1399-402 - PubMed
  2. Br J Pharmacol. 2001 May;133(1):83-8 - PubMed
  3. J Biol Chem. 2001 Nov 30;276(48):44926-35 - PubMed
  4. Leukemia. 2002 Apr;16(4):508-19 - PubMed
  5. Leukemia. 2002 Jul;16(7):1302-10 - PubMed
  6. J Biol Chem. 2003 Apr 18;278(16):14487-97 - PubMed
  7. Oncogene. 2004 Jan 8;23(1):278-88 - PubMed
  8. Nat Rev Cancer. 2004 Feb;4(2):97-105 - PubMed
  9. Br J Haematol. 2005 Mar;128(5):711-21 - PubMed
  10. Clin Cancer Res. 2005 Mar 1;11(5):1743-50 - PubMed
  11. Blood. 2005 Aug 15;106(4):1232-9 - PubMed
  12. Biochem Biophys Res Commun. 2005 Aug 12;333(4):1378-84 - PubMed
  13. Oncogene. 2006 Apr 6;25(15):2192-202 - PubMed
  14. Eur Heart J. 2006 Apr;27(7):802-7 - PubMed
  15. Acta Pharmacol Sin. 2006 Mar;27(3):360-6 - PubMed
  16. Blood. 2007 Oct 1;110(7):2659-66 - PubMed
  17. Int J Cancer. 2008 Feb 15;122(4):889-97 - PubMed
  18. Cancer. 2008 Jan 1;112(1):144-50 - PubMed
  19. Cancer Res. 2008 Jan 1;68(1):152-61 - PubMed
  20. Curr Mol Med. 2009 Jun;9(5):626-33 - PubMed
  21. Blood. 2009 Nov 26;114(23):4859-70 - PubMed
  22. Exp Cell Res. 2010 Jan 1;316(1):1-11 - PubMed
  23. Clin Exp Metastasis. 2009;26(8):1049-54 - PubMed
  24. Blood. 2010 Mar 11;115(10):1976-84 - PubMed
  25. Cancer Sci. 2010 Aug;101(8):1828-33 - PubMed
  26. Int J Biol Sci. 2010 Aug 03;6(5):419-27 - PubMed
  27. Mol Cancer Res. 2011 Mar;9(3):280-93 - PubMed
  28. J Transl Med. 2011 May 19;9:71 - PubMed
  29. Blood. 2012 May 31;119(22):5215-20 - PubMed
  30. Exp Ther Med. 2011 May;2(3):517-522 - PubMed
  31. Int J Biol Sci. 2013;9(1):55-66 - PubMed
  32. Nature. 2014 Feb 20;506(7488):328-33 - PubMed
  33. Matrix Biol. 2014 Jul;37:131-41 - PubMed
  34. Haematologica. 2014 Aug;99(8):1277-84 - PubMed
  35. Br J Cancer. 2015 Feb 17;112(4):729-38 - PubMed
  36. Cancer Lett. 2016 Oct 1;380(2):552-60 - PubMed
  37. Cell J. 2015 Fall;17(3):395-411 - PubMed
  38. Oncol Rep. 2016 Mar;35(3):1787-95 - PubMed
  39. Oncol Rev. 2015 Mar 09;9(1):261 - PubMed
  40. Life Sci. 2016 May 1;152:190-8 - PubMed
  41. Int J Hematol Oncol Stem Cell Res. 2016 Jul 1;10(3):120-9 - PubMed
  42. Rep Biochem Mol Biol. 2016 Apr;4(2):82-8 - PubMed
  43. Clin Transl Oncol. 2017 Sep;19(9):1059-1066 - PubMed
  44. Exp Oncol. 2017 Mar;39(1):30-35 - PubMed
  45. Exp Oncol. 2017 Mar;39(1):57-64 - PubMed
  46. Asian Pac J Cancer Prev. ;18(3):831-840 - PubMed
  47. Asian Pac J Cancer Prev. ;18(6):1655-1661 - PubMed
  48. Int J Hematol Oncol Stem Cell Res. 2017 Apr 1;11(2):148-157 - PubMed
  49. Blood. 1980 Aug;56(2):265-73 - PubMed
  50. Leukemia. 1997 Sep;11(9):1523-32 - PubMed

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