Study of the role of HSP90 in acute myeloid leukemia

Abstract

Review Heat shock proteins (HSPs) are a group of proteins whose expression are increased when the cells are exposed to elevated temperature or other stress. This increase in expression is transcriptionally regulated. A member of HSP family is HSP90, it is expressed in cytoplasm of most human cells.HSP90 exists in two forms HSP90 alpha, inducible and HSP90B, constitutive. HSP90 has a more restricted repertoire of client proteins mainly including protein kinase. It seems to be important for cellular proliferation, survival and adaptation to unfavorable microenvironments, and HSP90 inactivation results in inappropriate functioning and rapid degradation of its client proteins. Its normal chaperoning activity is strongly dependent on its co-chaperones, i.e. accessory proteins that interact with HSP90 and induce conformational changes. Aim The work was conducted to to evaluate the role of HSP90 in acute myeloid leukemia and find out its impact on prognosis. Subject and Method The subjects of this study were 90 patients with acute myeloid leukemia. The age of patients ranged from 4-67 years with a mean value of 43.367 ±15.146 years. They were 66 (73.33%) males, and 24 (26.67%) females. After diagnosis patients received chemotherapy and they were followed up for periods of 18 months with special attention to clinical and laboratory markers of remission and relapse and estimation of ate of first complete remission, date of relapse, death or last seen alive. Results In the current study, 90 newly diagnosed acute myeloid leukemic patients were investigated for HSP90 expression. High expression of HSP90 (>20%) was found in 48/90 (53.33%) AML patients and low expression of HSP90 (<20%) was found in 42/90 of patients (46.67%). In the current work, the age of selected patients ranged from 4-67 years with mean age of 43 years. In present study, it was found that 66/90 AML patients (73.33%) were males and 24/30 AML patients (26.67%) were females. Among the newly diagnosed AML patients; 43.33% had hepatomegaly, 50% had lymphadenopathy, 50% had pallor, 40% had purpura, and 60% had splenomegaly. There was no correlation between HSP90 expression and clinical features. As regard hematological finding, there was no significant association between HSP90 and Hb level. The present study showed mild to severe thrombocytopenia in almost all AML patients, There was no association between platelet count and HSP90 expression. There was a significant association of high total leucocytic count with high HSP90 expression. Circulating blasts in peripheral blood and blasts in BM were significantly associated with high expression of HSP90 in AML patients compared to low expressed HSP90 cases. There was statistically non significant relation between HSP90 expression and FAB subtype. There was a statistically significant association between high HSP90 expression and bad prognosis including relapse or death while the high remission rates were associated significantly with low expression of HSP90 cases.