Clinical Significance of ATM (Ataxia –Telangiectasia Mutated) and C-Myc Proteins in Multiple Myeloma Cases Treated with Valcade.
Zohreh Mohammad Taheri, Aleena Mansoor, Nizar Bahlis, Meer-Taher Shabani-Rad. University of Calgary, AB, Canada
Background: The ataxia-telangiectasia mutated (ATM) gene product is one of the proteins involved in DNA damage response (DDR). Mutation in ATM gene (Loss of protein) has been shown by molecular studies in a subsets of myeloma patients but not by protein expression, while it has been shown that expression of C-myc is associated with poor prognosis. To evaluate the expression of ATM and C-Myc proteins in a high risk multiple myeloma cases treated with Valcade and correlate the findings with TTP (time to progression) and OS (overall survival).
Design: Tissue microarray sections of initial diagnostic bone marrow sections from 39 multiple myeloma cases and 10 normal bone marrows were investigated for ATM and C-myc proteins expression by immunohistochemistry. The levels of protein expression (Loss for ATM and overexpression for C-myc) were correlated with TTP and OS of patients.
Results: The loss of ATM protein expression was observed in 17 out of 39 (40%) tissue samples, while the C-myc expression was identified in all cases at variable levels. Then the C-myc expression was categorized into 4 categories (0 to 3+). The group with high C-myc expression (3+) showed a better TTP (1.3 years) and OS (1.7 years) with P =0.09 and P =0.004 respectively). No correlation was found between loss of ATM protein expression and TTP as well as OS.
Conclusions: These finding indicate the overexpression of C-Myc is correlated with better response to treatment with Valcade. Although a subset of myeloma cases show loss of ATM protein expression, no correlation was found with Overall survival.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 251, Tuesday Morning