Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma

Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma （MM）.The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma （PRAME） in MM are unknown and were explored in this study.Methods The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction,and the prognostic value of PRAME was determined through retrospective survival analysis.PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME （＋）.Results Sixty-two patients （62.0％） overexpressed PRAME.PRAME overexpression showed no prognostic significance to either overall survival （n=100） or progression-free survival （PFS,n=96,all P ＞0.05） of patients.The patients were also categorized according to regimens with or without bortezomib.PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens （53.5％ vs.76.9％,P=0.071）.By contrast,it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens （77.5％ vs.63.9％,P ＞0.05）.When the patients were categorized into PRAME （＋） and PRAME （-） groups,treatment with bortezomib-containing regimens predicted a higher two-year PFS rate in PRAME （＋） patients （77.5％ vs.53.5％,P=0.027） but showed no significant effect on two-year PFS rate in PRAME （-） patients （63.9％ vs.76.9％,P ＞0.05）.Conclusion PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens.Bortezomib improves PFS in patients overexpressing PRAME.

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

Objective To investigate the expression of the preferentially expressed antigen of melanoma （PRAME） gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia （AL） and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics （gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype） of the patients were performed. Results The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia （AML, n=27）, and in 28.6% of the patients with acute lymphoblastic leukemia （ALL, n=7）, but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M~, 33.3% in M2, and 28.6% in M~. Gene expression was also found to be correlated with CDl5 and CD33 expression and abnormal karyotype, but not with age, gender; white blood count or percentage of blast cells. Conclusions The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia.