Molecular detection of survivin expression, antiapoptotic gene, and other prognostic markers, how they are correlated and how it could be of prognostic value in chronic myeloid leukemia patient

Egypt J Immunol. 2007;14(2):51-62.

Abstract

Chronic myeloid leukemia (CML) is a malignant disease of heampoitic stem cell resulting from clonal expansion of leukemic myeloid cells. Survivin is a recently identified member of the inhibitor of apoptosis protein family. The aim of the work is to analyze the expression of survivin in CML patient in chronic, accelerated and blastic phases and its correlation with other prognostic markers. The study included 50 CML patients (24 females and 26 males) and 10 healthy individuals (4 female and 6 male) as a control group. The studied groups were classified into group (I), 10 healthy individuals as a control group, group (II), 20 CML patients in chronic phase, Group (III), 15 CML patients in accelerated phase and Group (IV), 15 CML patients in blastic phase. The groups were subjected to clinical history and examination, CBC, ESR, BM aspiration (only patients), determination of serum survivin, IL-6 and beta2M levels by ELISA and survivin gene expression by quantitative real time PCR. There was a significant increase of survivin expression in patients as compared to controls (p < 0.001). The accelerated and blastic phases of the disease showed the highest significance (p < 0.001) than the chronic phase. Serum markers; survivin, IL6 and beta2M showed significant increase in the blastic phase, accelerated phase and chronic phase (p < 0.001, p < 0.001 and p < 0.001) respectively. A significant positive correlation was found between level of survivin expression and the other prognostic markers; high leucocytic count (r = 0.52), high peripheral basophile count (r= 0.81) and high peripheral blast cell count (r = 0.66), high level of serum survivin (r = 0.87), beta2 M (r = 0.76) and IL-6 (r= 0.90). On the other hand, a significant negative correlation was found between the survivin expression and hemoglobin concentration (r = 0.50). In conclusion, survivin is expressed in most cases of CML patients and its over expression is associated with bad prognosis.

MeSH terms

  • Adult
  • Analysis of Variance
  • Biomarkers, Tumor / blood*
  • Blast Crisis / blood
  • Blast Crisis / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Interleukin-6 / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Male
  • Microtubule-Associated Proteins / blood*
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • beta 2-Microglobulin / blood

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Interleukin-6
  • Microtubule-Associated Proteins
  • Survivin
  • beta 2-Microglobulin