Arsenic Trioxide Selectively Induces Apoptosis within the Leukemic Cells of APL Patients with t(15;17) Translocation Possibly through the Fas Pathway

Abstract

Background: Acute Promyelocytic Leukemia is a sub-type of acute myelogenous leukemia that occurs in about 10-15% of patients with AML. Approximately 20%-30% of these patients, who are treated with the current standard All Trans Retinoic Acid (ATRA) and Anthracyclin-based chemotherapy regimen, suffer relapse in less than a year. Arsenic trioxide (ATO) as a single agent can induce complete remission even in refractory and relapsed patients with few adverse effects. The investiga¬tors efforts regarding elucidation of the mechanisms of action underlying these clinical responses has shown that Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function, among which the most prominent ones are the induction of differentiation & apoptosis with low & high doses of arsenic, respectively. Purposes: In vivo apoptosis on these patients has not been evaluated yet and despite previous In vitro studies, which mostly reveal Fas/Apo1 is not expressed during ATO treatment, its in vivo expression has not been evaluated yet. Materials & methodes: In order to study the apoptotic pattern in leukemic cells of APL patients, we conducted a single-laser, triple-color flowcytometric experiment, to detect leukemic apoptotic cells in a heterogeneous population of bone mar¬row samples with the Annexin V & 7AAD technique. The Fas expression was also evaluated in promyelocyte population cells in a dual color panel. Results & Conclusion: A substantial Apoptosis was selectively detected in Promyelocytic cells during the early and middle stages of treatment and the concurrent Fas expression indicates its involvent in Apoptosis induced by Arsenic Trioxide.

Keywords

• Acute Promyelocytic Leukemia
• Arsenic trioxide
• Apoptosi
• Fas/Apo1
• Flowcytometry