Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

  • Ozbas-Gerceker, Filiz (Department of Biology, Section of Molecular Biology, Faculty of Arts and Science) ;
  • Bozman, Nazli (Department of Biology, Section of Molecular Biology, Faculty of Arts and Science) ;
  • Kok, Selcuk (Department of Biology, Section of Molecular Biology, Faculty of Arts and Science) ;
  • Pehlivan, Mustafa (Department of Internal Medicine, Section of Hematology) ;
  • Yilmaz, Mehmet (Department of Internal Medicine, Section of Hematology) ;
  • Pehlivan, Sacide (Department of Medical Biology, Faculty of Medicine, University of Gaziantep) ;
  • Oguzkan-Balci, Sibel (Department of Medical Biology, Faculty of Medicine, University of Gaziantep)
  • Published : 2013.11.30


Hematological malignancies (HM) are a group of neoplasms derived from the cells of the bone marrow and lymphatic system. Genetic factors leading to susceptibility to HM have been investigated for years but little is known yet. Low molecular weight polypeptide (LMP) 2 and LMP7 genes are important subunits of the immunoproteasome and play significant role in antigen presentation. The polymorphisms of LMP genes have been reported to be risk factors for various types of diseases. The aim of this study was to investigate the association of LMP2 and LMP7 polymorphisms with the occurrence of particular types of HM. A total of 132 patients with HM and 130 control subjects were investigated. No significant difference was obtained in the distribution of genotype and allele frequencies of LMP7 gene in HM patients and the control group. On the other hand, the prevalence of LMP2-AA genotype was found to be higher in acute myeolid leukemia (AML) patients while it was significantly lower in multiple myeloma (MM) cases than in the control subjects. Our results suggested that LMP7 could not be a risk factor for susceptibility to HM, whereas LMP2 polymorphisms could play a role in the development of AML and MM.


LMP2;LMP7;hematological malignancy;polymorphism;Turkish


  1. Atkins D, Breuckmann A, Schmahl GE, et al (2004a). MHC class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma. Int J Cancer, 109, 265-3.
  2. Atkins D, Ferrone S, Schmahl GE, et al (2004b). Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma? J Urol, 171, 885-9.
  3. Cao B, Tian X, Li Y, et al (2005). LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. Carcinogenesis, 26, 1280-4.
  4. Crowther-Swanepoel D, Broderick P, Di Bernardo MC, et al (2010). Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat Genet, 42, 132-6.
  5. Descatha A, Jenabian A, Conso F, et al (2005). Occupational exposures and haematological malignancies: overview on human recent data. Cancer Causes Control, 16, 939-3.
  6. Di Bernardo MC, Crowther-Swanepoel D, Broderick P, et al (2008). A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nat Genet, 40, 1204-10.
  7. Fellerhoff B, Gu S, Laumbacher B et al (2011). The LMP7-K allele of the immunoproteasome exhibits reduced transcript stability and predicts high risk of colon cancer. Cancer Res, 71, 7145-4.
  8. Gromme M, Neefjes J (2002). Antigen degredation or presentation by MHC class I molecules via classical and non-classical pathways. Mol Immunol, 39, 181-2.
  9. Houlston RS (2010). Low-penetrance susceptibility to hematological malignancy. Curr Opin Genet Dev, 20, 245-0.
  10. Hoves S, Aigner M, Pfeiffer C, et al (2009). In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray. Leukemia, 23, 877-5.
  11. Irigaray P, Newby JA, Clapp R, et al (2007). Life style related factors and environmental agents causing cancer: an overview. Biomed Pharmacother, 61, 640-8.
  12. Kageshita T, Hirai S, Ono T, et al (1999). Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Am J Pathol, 154, 745-4.
  13. Liu Y, Luo YR, Lu X, et al (2011). Association analysis of polymorphisms of porcine LMP2 and LMP7 genes with hematological traits. Mol Biol Rep, 38, 4455-60.
  14. Mehta AM, Jordanova ES, van Wezel T, et al (2007). Genetic variation of antigen processing machinery components and association with cervical carcinoma. Genes Chromosomes Cancer, 46, 577-6.
  15. Mehta AM, Jordanova ES, Kenter GG, et al (2008). Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother, 57, 197-6.
  16. Meissner M, Reichert TE, Kunkel M, et al (2005). Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin Cancer Res, 11, 2552-60.
  17. Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215.
  18. Papaemmanuil E, Hosking FJ, Vijayakrishnan J, et al (2009). Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet, 41, 1006-10.
  19. Ritz U, Momburg F, Pilch H, et al (2001). Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol, 19, 1211-20.
  20. Rueda-Faucz F, Probst CM, Petzl-Erler ML (2000). Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversity. Eur J Immunogenet, 27, 5-6.
  21. Seliger B, Cabrera T, Garrido F, et al (2002). HLA class I antigen abnormalities and immune escape by malignant cells. Semin Cancer Biol, 12, 3-13.
  22. Seliger B, Ritz U, Ferrone S (2006). Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer, 118, 129-8.
  23. Seliger B, Stoehr R, Handke D, et al (2010). Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer. Cancer Immunol Immunother, 59, 529-0.
  24. Sugimoto Y, Kuzushita N, Takehara T, et al (2002). A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C. J Viral Hepat, 9, 377-4.
  25. Tang Q, Zhang J, Qi B, et al (2009). Downregulation of HLA class I molecules in primary oral squamous cell carcinomas and cell lines. Arch Med Res, 40, 256-3.
  26. Van Kaer L (2002). Major histocompatability complex class-I restricted antigen presenting and presentation. Tissue Antigens, 60, 1-9.
  27. Vasuri F, Capizzi E, Bellavista E, et al (2010). Studies on immunoproteasome in human liver. Part I: absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis. Biochem Biophys Res Commun, 397, 301-6.
  28. Weng Y, Lu L, Yuan G, et al (2012). p53 codon 72 polymorphism and hematological cancer risk: an update meta-analysis. PLoS ONE, 7, 45820.
  29. Zheng F, Hasim A, Anwer J, et al (2013). LMP gene promoter hypermethylation is a mechanism for its down regulation in Kazak's esophageal squamous cell carcinomas. Mol Biol Rep, 40, 2069-5.

Cited by

  1. Elevated Serum Ferritin Levels in Patients with Hematologic Malignancies vol.15, pp.15, 2014,
  2. Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study pp.1792-1082, 2015,
  3. Genetic characterisation of 19 autosomal STR loci in a population sample from the Southeastern Anatolia Region of Turkey vol.45, pp.2, 2018,