Fas (CD95) expression as a prognostic marker in acute leukemia and blastic transformation phase in chronic myeloid leukemia

Abstract

Introduction Fas is expressed on a majority of human leukemic cells. Fas-mediated cell death is involved in drug-induced apoptosis in various cell types. Hence, failure of apoptosis could lead to chemoresistance and may therefore have an impact on clinical outcome. The aim of the present study was to evaluate the percentage of Fas receptor expression on blast cells in patients with adult acute leukemia and blastic transformation phase of chronic myeloid leukemia (CML-BT), and to find out the impact of Fas expression on prognosis. Subjects and methods The participants of this study were 80 adult acute leukemia patients classified as follows: 40 acute myeloid leukemia (AML) patients, 32 ALL patients, and eight CML-BT patients. In addition, 10 age-matched and sex-matched healthy controls were also included in the study. Patients with acute leukemia were studied at diagnosis and after treatment. The diagnosis of AML, ALL, and CML-BT was assessed by morphological study, cytochemical analysis, and immunophenotyping of peripheral blood (PB) and bone marrow aspirate according to FAB classification. Fas expression on blast cells from bone marrow aspirate or PB samples of the patients or on normal monocytes, granulocytes, and lymphocytes obtained from PB samples of controls was measured using flow cytometry. The correlation between prognostic markers (age, sex, total leukocytic count, serum lactate dehydrogenase (LDH), and cytogenetic risk categories) and Fas expression levels on blast cells of leukemic patients at diagnosis was ascertained. After treatment, patients were followed up for periods ranging from 25 to 31 months. Results Fas expression was seen to be the highest on control monocytes (31.2 ± 6.95%), followed by granulocytes (24.8 ± 7.61%), whereas lymphocytes expressed the lowest levels (17.1 ± 4.01%) with a highly statistically significant difference ( P P P = 0.039) in T-ALL (55.15 ± 7.8%) in comparison with precursor B-ALL (34.47 ± 5.76%). CML-BT patients were all transformed to AML type and expressed Fas with a mean of 31.0 ± 7.63%. Only three of them (37.5%) were Fas negative and the remaining five (62.5%) were Fas positive. The percentage of Fas-positive patients was 0% (0/1) in M1, 50% (2/4) in M2, 100% (1/1) in M4, and 100% (2/2) in M5. No significant differences could be detected between Fas-positive and Fas-negative patients with respect to baseline patient characters (age, sex, total leukocytic count, serum LDH levels, and cytogenetic risk category). Highly significant correlation was found between Fas-positive expression and response to therapy ( P P = 0.049). Overall survival between Fas-positive and Fas-negative patients was statistically significant in AML, ALL, and CML-BT patients ( P = 0.001, 0.002, and 0.002, respectively). Conclusion The mean value of Fas expression by blast cells from AML, ALL, and CML-BT patients at diagnosis was 41.72 ± 10.3, 42.87 ± 11.5, and 31 ± 7.63%, respectively. We can conclude that Fas receptor expression on blast cells from ALL, AML, and CML-BT patients could serve as an independent prognostic factor and help in monitoring the outcome of chemotherapy.