FHIT Gene Expression in Acute Lymphoblastic Leukemia and its Clinical Significance

  • 발행 : 2016.01.11


Background: To investigate the expression of the fragile histidine triad (FHIT) gene in acute lymphoblastic leukemia and its clinical significance. Materials and Methods: The level of expressed FHIT mRNA in peripheral blood from 50 patients with acute lymphoblastic leukemia (ALL) and in 50 peripheral blood samples from healthy volunteers was measured via RT-PCR. Correlation analyses between FHIT gene expression and clinical characteristics (gender, age, white blood count, immunophenotype of acute lymphoblastic leukemia and percentage of blast cells) of the patients were performed. Results: The FHIT gene was expressed at $2.49{\pm}7.37$ of ALL patients against $14.4{\pm}17.9$ in the healthy volunteers. The difference in the expression levels between ALL patients and healthy volunteers was statistically significant. The rate of gene expression did not significantly vary with immunophenotype subtypes. Gene expression was also found to be correlated with increase of total leukocyte and decrease in platelets, but not with age, gender, immunophenotyping or percentage of blast cells. Conclusions: FHIT gene expression is low in acute lymphoblastic leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute lymphoblastic leukemia.


  1. Alison Walker and Guido Marcucci (2012). Molecular prognostic factors in cytogenetically normal acute myeloid leukemia. Expert Rev Hematol, 5, 547-58.
  2. Chen Xu, Hui Zhang, Ping Li, et al (2013). Gene expression of WWOX, FHIT and p73 in acute lymphoblastic leukemia. Oncology Letters, 6, 963-9.
  3. Cobaleda C, Sanchez Garcia I (2009). B-cell acute lymphoblastic leukaemia: Towards understanding its cellular origin. Bioessays, 31, 600-609.
  4. Gemma Toledo, Jesus Javier Sola, Maria Dolores Lozano, et al (2004). Loss of FHIT protein expression is related to high proliferation, low apoptosis and worse prognosis in non-small-cell lung cancer. Modern Pathology, 17, 440-8
  5. Gokbuget N, Hoelzer D (2009). Treatment of adult acute lymphoblastic Leukemia. Semin Hematol, 46, 64-75.
  6. Gomes AM, Soares MV, Ribeiro P, et al (2014). Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and Constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels. Haematologica, 99, 1062-8
  7. Hagop M. Kantarjian, Moshe Talpaz, Susan O'Brien, et al (1999). Significance of FHIT expression in chronic myelogenous leukemia. Clinical Cancer Research, 4059, 4059-64.
  8. Hallas C, Albitar M, Letofsky J, etal (1999). Loss of FHIT expression in acute lymphoblastic leukemia. Cin Cancer Res, 5, 2409-14.
  9. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real- time quantitative PCR and the 2(-Delta Delta CT) method. Methods, 25, 402-8
  10. Marks DI (2010). Treating the "older" adult with acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program, 13-20.
  11. Mona M. Taalab, Iman M. Fawzy, Enas F. Gouda, etal (2014). BAALC gene expression in adult b-precursor acute lymphoblastic leukemia: impact on prognosis. J Blood Disorders Transf, 5.
  12. Shichun Zheng, Xiaomei Ma, Luoping Zhang, et al (2004). Hypermethylation of the 5_ CpG Island of the FHIT Gene Is Associated with Hyperdiploid and Translocation-Negative Subtypes of Pediatric Leukemia. Cancer Research, 64, 2000-6
  13. Wang HL, Zhou PY, Liu P, et al (2014). Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis. Tumour Biol, 35, 6815-21
  14. Waters C, Saldivar J, Hosseini SA, et al (2014). The FHIT gene product: tumor suppressor and genome “caretaker”. Cell Mol Life Sci, 71, 4577-87
  15. Zhiwei Chang, Weijie Zhang, Zhijun Chang, et al (2015). Expression characteristics of FHIT, p53, BRCA2 and MLH1 in families with a history of oesophageal cancer in a region with a high incidence of oesophageal cancer. Oncology Letters, 9, 430-6
  16. Zhou Y, Slack R, Jorgensen JL, et al (2014). The effect of peritransplant minimal residual disease in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk, 14, 319-26

피인용 문헌

  1. FHIT promoter DNA methylation and expression analysis in childhood acute lymphoblastic leukemia vol.14, pp.4, 2017,