Quantitative expression of the eukaryotic translation initiation factor 4E (eIF4E) in egyptian acute leukemia patients and its clinical significance
Purpose: The eukaryotic translation initiation factor eIF4E is part of the eIF4F protein complex, which includes, in addition to eIF4E, eIF4G (a scaffolding protein) and eIF4A (an ATP-dependent RNA helicase). The eukaryotic translation initiation factor eIF4E is a potent oncogene elevated in many cancers including leukemias.
Methods: In this study, the expression level of eIF4E gene was analyzed in 20 normal healthy controls and 64 patients with de novo acute leukemia (33 Acute myeloid leukemia (AML) and 31 Acute lymphoblastic leukemia (ALL)) using a real-time quantitative reverse-transcriptase polymerase chain reaction (RTQ-PCR) to investigate a possible relation, association or correlation with the clinical features at diagnosis, such as age, gender, lineage, hemoglobin (Hb), total leucocytic count (TLC), platelet count and bone marrow (BM) blast cell infiltration as well as its effect on patients̒ outcome.
Results: Comparing AML and ALL patients as regards their clinical and laboratory data showed no statistical significance for TLC and hemoglobin (p-0.838 and 0.920) respectively, but was of statistically significant difference for platelets (p = 0.022) and bone marrow blasts percentage (p = 0.007). Comparison between the 2 groups as regards eIF4E level was of no statistically significant difference, p-value being (p = 0.257) but there was statistically significant difference between eIF4E expression level in AML/Control (p = 0.002), ALL/Controls (p = 0.025). Also analysis of overall survival (OS) time and disease free survival (DFS) in each group and its relation to eIF4E gene showed no statistical significance (p = 0.843 and 0.310) respectively in AML group and (p = 0.971 and no p-value for DFS in ALL as all cases remained alive except for one case while 3 cases were relapsed) in ALL group. Correlation studies showed no significant correlation between AML group and eIF4E gene level as regards age, TLC, hemoglobin and platelets (r = -0.064, p = 0.722; r = 0.062, p = 0.732; r = 0.068, p = 0.712; and r = -0.318, p = 0.071) respectively, while there was significant positive moderate correlation on comparing bone marrow blast% and eIF4E gene level (r = 0.545 and p = 0.001). There was no significant correlation between ALL group and Eif4e gene level as regards age, TLC, hemoglobin, platelets and bone marrow blasts% (r = -0.214, p = 0.248; r = 0.175, p = 0.347; r = -0.056, p = 0.766; r = -0.072, p = 0.700; and r = -0.0004, p = 0.983) respectively.
Conclusion: eIF4E was found to be elevated in acute leukemia patients in relation to normal controls and its levels were more in myeloid than lymphoid leukemia and positively correlated with the blast percentage in AML thus its level may contribute to leukemogenesis. eIF4E levels and translation initiation may be an attractive target for anticancer therapeutics.
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