Prognostic relevance of telomerase and Bcl-2 in acute myeloid leukemia

ABSTRACT

Prognosis of AML patients is influenced by both clinical and genetic markers. As therapy and supportive care improves, the intrinsic biologic characteristics of the patient's leukemia become the dominant factor in determining prognosis. Some reports suggest that telomerase and Bcl-2 may have a prognostic relevance in AML. The objective of this study was to evaluate the prognostic relevance of Telomerase activity and serum level of Bcl-2 in correlation with the disease outcome of AML patients. The study included 63 newly diagnosed cases of acute myeloid leukemia who presented to the Medical Oncology department at the National Cancer Institute, Cairo University. All patients were adults below the age of 60 years. Blood samples were taken from all patients to assess telomerase activity and Bcl-2 levels prior to the administration of anti-neoplastic treatment as well as from ten healthy controls. Assessment of telomerase activity was done using PCR-ELISA technique and evaluation of Bcl-2 serum level was done using ELISA. Patients were followed up for 3 years. Assessment of prognostic factors in the present study included three main independent parameters cytogenetics abnormalities [20 cases], immunophenotyping [63 cases] and hyperleukocytosis [63 cases]. Patients were also grouped according to the presence of independent prognostic factors into a poor prognosis group and a non-poor prognosis group. Using this classification half the patients [29 patients 46%] were categorized in the poor prognosis group. Thirty six percent of patients had hyperleukocytosis [TLC >/= 100,000/micro l], 38% expressed unfavorable immunophenotypic markers [CD34 positivity and/or biphenotypic leukemia's markers], while 3 patients had a poor karyotypic profile [11q23, t [9; 22], del 5q]. The complete remission rate was 57% and the overall median time to CR was 31 days. The 2-year and 3-year overall survival rates were 32.5% and 23.5% respectively. While the 2 and 3-year disease-free survival rates were 21.6% and 18% respectively. We found no correlation between the presence of adverse prognostic factors and time to CR, overall survival or disease-tree survival rates. However, patients in the poor prognosis group showed an inferior 2-year disease-free survival [12% versus 34%; p=0.02]. The median level of telomerase activity for AML patients was 0.40 U [0.38 to 0.56]. We found a significant negative correlation between CR rate and telomerase activity [p=0.019] but not with time to CR, or the 2-year overall survival. Lower levels of telomerase activity were associated with a significantly better disease free survival at 1 year when compared to higher levels [34% versus 10%; p=0.012]. There was also a highly significant correlation between telomerase activity and the poor prognosis group [p=0.0001]. The median serum level of Bcl-2 for patients in the present study was 204 U/mL. Bcl-2 levels correlated negatively with CR rate [p=0.06]; but did not correlate with time to CR. Bcl-2 levels less than 200 U/mL were associated with better 2-year overall survival and 1-year disease-free survival [p=0.07 and p=0.005]. There was a highly significant correlation between Bcl-2 and prognosis group [p=0.0001], the presence of hyperleukocytosis [p=0.0001] and CD 34 positivity [p= 0.011]. Patients with more than one poor prognostic criterion had a tendency for lower overall survival rate at 1 year [24% versus 42%; p=0.094] and significantly lower disease-free survival rate at 1 year [24% versus 50%; p=0.036]. There was a significant correlation between telomerase activity levels and Bcl-2 level in the serum of AML patients [r=0.623, p< 0.0001]. Telomerase activity levels and Bcl-2 levels correlate significantly with disease-free survival in AML patients. Further studies would be needed to establish their role in the prognosis of this disease and to determine if an association between telomerase activity and the anti-apoptotic pathway exists