Nestin expression throughout multistep pathogenesis of multiple myeloma

Abstract

SummaryThe stem cell marker nestin (NES) is found in dividing cells of developing and regenerating tissues. Upon terminal differentiation, NES expression is diminished but may be re-expressed following injury or in cancer. Surprisingly, we recently confirmed NES as a tumour-specific marker for mature CD138 + 38 + plasma cells (PC) in multiple myeloma (MM). The present study analysed NES expression throughout the spectrum of MM developmental stages, starting with individuals with no haematological malignancy, through monoclonal gammopathy of undetermined significance (MGUS) and MM to plasma cell leukaemia (PCL) and MM cell lines. NES was analysed in bone marrow PC of 163 MM, four PCL and nine MGUS patients, 10 individuals with no haematological malignancy and 6 myeloma cell lines (OPM-2, RPMI-8226, MOLP-8, U-266, EJM, NCI-H929) by flow cytometry and/or real-time polymerase chain reaction or immunochemistry. We observed a tendency of increased NES expression in parallel with disease progression. NES was evaluated as a reliable marker for accurate discrimination between MM patients and the control group. High NES levels were strongly associated with the presence of 1q21 gain. For the first time, NES was demonstrated to predict worse response to conventional therapy/novel agents. These results suggest that NES might become a useful clinical parameter with an important role in MM pathogenesis.

Prognostic Value and Efficacy Evaluation of Novel Drugs for Multiple Myeloma Patients with 1q21 Amplification (Amp1q21) Only: A Systematic Review of Randomized Controlled Trials

“…Despite the evidence provided by above study, we also found the direct evidence that detection rate in relapse MM patients is higher than that in NDMM patients all the time [5,21,28]. In an early study, the stem cell marker nestin strongly associated with the presence of 1q21 gain may play an important role in MM relapse [29]. Besides, a study in Beijing analysis a gene expression microarrays of 1878 MM patients and found that with the increase of the amplification level of 1q21, the expression level of BCAR3 which is a protein-coding gene associated with many tumors showed an overall downward trend, interestingly, the expression of BCAR3 gene was different statistically in the non-relapse group and the relapse group, and the expression in the non-relapse group was notably higher than that in the relapse group (P = 0.0023) [14].…”

Nestin as a marker of cancer stem cells

“…40 , 41 Interestingly, the use of nestin as a predictive marker of a poor response to conventional therapy and to novel therapeutic agents was recently reported for multiple myeloma. 42 …”

“… 44 Furthermore, an association between increased nestin expression and the pathogenesis of multiple myeloma has been reported. 42 …”

Prognostic Biomarkers in the Progression From MGUS to Multiple Myeloma: A Systematic Review

“…Since NES levels correlate with tumor grade and represent a marker of cancer stem cells, it is presumed that NES also plays a role in carcinogenesis. Svachova et al (44) analyzed the occurrence of NES throughout the pathogenesis of MM, including patients with no hematological malignancy and MGUS. They showed that NES is differentially expressed in both patients with MM and MGUS.…”