نقش ارسنیک در القای آپوپتوزیس از مسیر Fas در بیماران لوسمی حاد پرومیلوسیتی با جابه‌جایی کروموزومی

Acute promyelocytic leukemia (APL) is a sub-type of acute myelogenous leukemia (AML) which 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 anthracyclines-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. Studies conducted by investigators to elucidate the mechanisms of action underlying these clinical responses have shown that Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function among which differentiation induction with low dose and apoptosis induction with high dose are the most prominent mechanisms. Despite previous in vitro studies, which mostly revealed that Fas/Apo 1 expression is unchanged during ATO treatment, in vivo expression of this classical receptor for apoptosis induction has not been evaluated yet. In order to study the apoptotic pattern in leukemic cells of these patients, a single-laser triple-color flowcytometric method was conducted by Annexin V and 7AAD technique, to detect leukemic apoptotic cells in a heterogeneous population of bone marrow samples. Fas/Apo 1 expression was also evaluated in promyelocyte population cells in a dual color panel. A substantial apoptosis was selectively detected in promyelocytic cells during the first and the second weeks following treatment and the concurrent Fas expression indicated its involvement in apoptosis induced by arsenic trioxide.