Young female patients with multiple myeloma have low occurrence of osteolytic lesion.

Abstract

Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders. We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. The presence or absence of OL was confirmed by X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) examination. We also downloaded MM patients' published gene expression profiles and performed microarray-based analyses to identify differentially regulated genes and signaling pathways. Finally, we examined target gene expressions in MM bone marrow (BM) biopsies through immunohistochemistry (IHC). We calculated the frequency of OL in female and male MM patients with different age cut-offs. From West China Hospital data, we found that in young female MM patients aged under 55, the frequency of OL was 16.67%, significantly lower than the frequencies in other groups of patients (young males: 34.38%; old males: 31.04%; old females: 29.24%; p < .05). The same was true in another independent MM cohort. Microarray-based analyses showed that Microtubule Associated Serine/Threonine Kinase Family Member 4 (MAST4), an estrogen-responsive gene, expression was up-regulated in MM patients without OL and in young female MM patients (p < .05). The expression of MAST4 in MM BM was confirmed by IHC. The perspective of cell signaling network suggested that MAST4 might interact with phosphatase and tensin homolog (PTEN) and control the expression of a panel of osteoclast-regulatory cytokines, such as TNFSF11 and CCL2. Young female (<55 years) MM patients have significantly lower OL frequency than other groups. MAST4 gene expression is thought to be associated with this phenomenon.