Skip to main content

Advertisement

Log in

Glutathione S-transferase genotypes and numerical chromosomal aberrations in myeloid neoplasms

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

The aim of the present study was to detect the frequency of monosomy 7 and trisomy 8 in myeloid disorders (acute myeloblastic leukemia (AML), myelodysplastic syndrome (MDS)), their association with GSTT1 and GSTM1 null genotypes, and their prognostic impact. The study included 50 patients with AML and MDS; monosomy 7 and trisomy 8 detection was done by interphase fluorescence in situ hybridization, and glutathione S-transferase (GST) genotyping was done by multiplex PCR. Monosomy 7 was present in 13–30 % of AML and MDS, respectively. A statistically significant relation was found between monosomy 7 and remission failure. Trisomy 8 was found in 10–15 % of AML and MDS. No significant association was found between response to treatment and trisomy 8. There was significant correlation between GSTT1 null/GSTM1 null genotype and poor response to treatment (p < 0.005). There was positive correlation between complete remission and both wild GST genotypes. In the whole patient group, a statistically significant association was found between GSTT null genotypes and monosomy 7 (p = 0.003). No significant association was found between trisomy 8 and specific GST genotypic polymorphism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bernasconi P, Cavigliano PM, Boni M, Calatroni S, Klersy S, Giardini I et al (2003) Is FISH a relevant prognostic tool in myelodysplastic syndromes with a normal chromosome pattern on conventional cytogenetics? A study on 57 patients. Leukemia 17:2107–2112

    Article  CAS  PubMed  Google Scholar 

  • Brozek I, Babinska M, Kardas I, Wozniak A, Balcerska A, Hellmann A, Limon J (2003) Cytogenetic analysis and clinical significance of chromosome 7 aberrations in acute leukemia. J Appl Genet 44:401–412

    PubMed  Google Scholar 

  • Byrd JC, Lawrence D, Arthur DC, Pettenati MJ, Tantravahi R, Qumsiyeh M et al (1998) Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from cancer and leukemia group B 8461. Clin Cancer Res 4:1235–1241

    CAS  PubMed  Google Scholar 

  • Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al (2002) Pretreatment cytogenetic abnormalities are predictive of induction success. Cumulative incidence of relapse and overall survival in adult patients with de novo acute myeloid leukemia results from cancer and leukemia group B (CALGB 8461). Blood 100:4325–4336

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD et al (1996) Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 347:295–297

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Pasquini M, Hong B, Dehart S, Tsai S (2005) The human penumbra gene is mapped to a region on chromosome 7 frequently deleted in myeloid malignancies. Cancer Genetics and Cytogenetics 162:95–98

    Article  CAS  PubMed  Google Scholar 

  • Cheson BD, Cassileth PA, Head DR et al (1990) Report of the National Cancer Institute-sponsored workshop on definition of diagnosis and response in AML. J Clin Oncol 8:813

    CAS  PubMed  Google Scholar 

  • Crump C, Chen C, Appelbaum FR, Kopecky KJ, Weiss NS (2000) Glutathione S-transferase theta 1 gene deletion and risk of acute myeloid leukemia. Cancer Epidemiol Biomarkers Prev 9(5):457–460

    CAS  PubMed  Google Scholar 

  • Dahabreh IJ, Giannouli S, Gota V, Voulgarelis M (2010) GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta-analysis. Int J Cancer 126:1716–1723

    CAS  PubMed  Google Scholar 

  • Dastugue N, Payen C, Lafage-Pochitaloff M, Bernard P, Leroux D, Huguet-Rigal F et al (1995) Prognostic significance of karyotype in de novo adult acute myeloid leukemia. Leukemia 9:1491–1498

    CAS  PubMed  Google Scholar 

  • Elliott MA, Letendren L, Hanson CA, Tefferi A, Dewald GW (2002) The prognostic significance of trisomy 8 in patients with acute myeloid leukemia. Leuk Lymphoma 43:583–586

    Article  PubMed  Google Scholar 

  • Grimwade D, Walker H, Oliver F, Wheatly K, Harrison C, Harrison G et al (1998) The importance of diagnostic cytogenetics on outcome in AML analysis of 1,612 patients entered into the MRC AML to trial. Blood 92:2322

    CAS  PubMed  Google Scholar 

  • Heba N, Abdelrazik HN, Hala Farawila, Mai sherif, mervat El Ansary (2006) Molecular characterization of chromosome 7 in AML and MDS patients. African Journal of Health Sciences: vol 13, N3-4, 33–42

  • Heim S, Mitelman F (1992) Cytogenetic analysis in the diagnosis of acute leukemia. Cancer 70:1701

    Article  CAS  PubMed  Google Scholar 

  • Ketterer B, Taylor J, Meyer D, Pemble P, Coles B, Chulin X et al (1993) Some functions of glutathione transferases. In: Tew KJ, Pickett CB, Mantle TJ, Mannervik B, Hayes JD (eds) Structure and function of glutathione transferases. CRC press, Boca Raton, pp 15–27

    Google Scholar 

  • Kibbelaar RF, Mulder JWR, Dreef EJ, Klwin (1993) Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization. Am Soc Hematol

  • Korke M, Takeuchi S, Yokota J, Park S, Hatta Y, Miller CW, Suruoka N, Koeffler HP (1997) Frequent loss of heterozygosity in the region of the D7S523 locus in advanced ovarian cancer. Genes Chromosomes Cancer 19:1–5

    Article  Google Scholar 

  • Najfeld V (2012) Conventional and molecular cytogenetic basis of hematologic malignancies. Chapter 55 pp 810–821. In: Hematology basic principles and practice. Churchill Livingstone, Philadelphia

  • Norppa H, Hirvonen A, Jarventaus H, Uuskula M, Tasa G, Ojajarvi A, Sorsa M (1995) Role of GSTT1 and GSTM1 genotypes in determining individual sensitivity to sister chromatid exchange induction by diepoxybutane in cultured human by lymphocytes. Carcinogenesis 16:1261–1264

    Article  CAS  PubMed  Google Scholar 

  • Ohyashiki K, Sasao I, Ohyashiki JH, Murakami T, Tauchi T, Iwabuchi A et al (1992) Cytogenetic and clinical findings of myelodysplastic syndromes with a poor prognosis. An experience with 97 cases. Cancer 70:94–99

    Article  CAS  PubMed  Google Scholar 

  • Paulsson K, Sall T, Fioretos T, Mitelman F, Johansson B (2001) The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology. Cancer Genet Cytogenet 130:160–165

    Article  CAS  PubMed  Google Scholar 

  • Pulsoni A, Pagano L, Latagliate R, Casini M, Cerri R, Crugnola M, De Paoli L, Di Bone E, Invernizzi R, Marmont F, Petti MC, Rigolin G, Ronco F, Spadano A, Tosti E, Visani G, Mandelli F (2004) Survival of elderly patients with acute myeloid leukemia. Haematologica 89:296–302

    PubMed  Google Scholar 

  • Rollinson S, Roddam P, Kane E, Roman E, Cartwright R, Jack A et al (2000) Polymorphic variation within the glutathione S-transferase genes and risk of adult acute leukemia. Carcinogenesis 21:43–47

    Article  CAS  PubMed  Google Scholar 

  • Sasai Y, Horiike S, Misawa S, Kaneko H, Kobayashi M, Fujii H et al (1999) Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia. Leuk Res 23:975–981

    Article  CAS  PubMed  Google Scholar 

  • Smith A, Worrillow L, Allan J (2007) A common genetic variant in XPD associates with risk of 5q- and 7q-deleted acute myeloid leukemia. Blood 109(3):1274–1279

    Google Scholar 

  • Timothy J, Chevassut T, Mufti GJ (2011) The myelodysplastic syndromes. In: Post graduate haematology, 6th edn. Wiley-Blackwell, Oxford, pp 509–510

  • Voso M, D’ALO F, Putzulu R, Mele L, Leone G (2002) Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Blood 100:8

    Article  Google Scholar 

  • Wolman SR, Gundacker H, Appelbaum FR, Slovak ML (2002) Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia. A southwest oncology group study. Blood 100:29–35

    Article  CAS  PubMed  Google Scholar 

  • Yates JW, Wallace JH, Ellison RR et al (1973) Cytosine arabinoside and Daunorubicin therapy in acute non lymphocytic leukemia (part 1). Cancer Chemoth Rep 57:485

    CAS  Google Scholar 

  • Zhang Y, Yang L, Li R, Zhang L, Zhang MR, Xiao ZJ (2006) The effects of glutathione S-transferase (GSTT1 and GSTM1) genes polymorphisms on treatment efficacy and prognosis of acute myeloid leukemia. Chinese J Intern Med 45:213–216

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mona W. Ayad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ayad, M.W., Nafea, D.A. Glutathione S-transferase genotypes and numerical chromosomal aberrations in myeloid neoplasms. Comp Clin Pathol 23, 1023–1029 (2014). https://doi.org/10.1007/s00580-013-1737-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-013-1737-1

Keywords

Navigation