Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained incurable. It accounts for 1.8% of all malignancies and is the second most common hematologic malignancy.1–2 The prognosis of this disease was poor around ten years ago, but a better understanding of MM, alongside new treatments, helps to improve the situation.1 However, due to huge heterogeneity in the response rate and survival outcomes, the course of MM is heterogeneous, so the survival time widely ranges from a few months to more than 10 years.3 High-risk MM is associated with elevated serum lactate dehydrogenase, high-risk cytogentics and extramedullary disease.4 Nevertheless, no immunohistochemical (IHC) predictive and prognostic marker of MM has been constructed yet.
Two of the biggest challenges associated with MM are acquired drug resistance and relapse, which make MM incurable yet. CXCR4 an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF1), reportedly is most widely expressed in tumors.5 A meta-analysis shows that high CXCR4 expressions in esophagus, gastric and colorectal cancers all predict a worse prognosis.6 Reportedly, when Bortezomib-resistant MM cells express less CXCR4, plasma cells excape from bone marrow extramedullary metastasis in MM mice and MM patients.7 The CXCR4/SDF1 axis plays a pivotal role in the proliferation, invasion, dissemination and drug resistance of MM cells.8,9 Despite wide reporting, the prognostic value of CXCR4 expression in MM remains controversial.
Extramedullary multiple myeloma (EMM) can thrive and grow independent of the bone marrow microenvironment, resulting in a high-risk state associated with increased proliferation, evasion of apoptosis and treatment resistance.10 High-dose therapy with autologous stem-cell transplantation (ASCT) can overcome the negative prognostic impact of extramedullary disease in younger selected patients.11,12 Unfortunately, the median age at diagnosis of MM is 69 years, but three-quarters of patients are diagnosed above the age of 55 years.13 Even worse, most patients have no access to high-dose chemotherapy.
Despite the improved survival in most MM patients over recent decades, outcomes are generally poor when EMM develops. Possible mechanisms of extramedullary spread include decreased adhesion molecule expression and downregulation of chemokine receptors. This study, presents for the first time that reduced CXCR4 expression is associated with the extramedullary subentity and predicted poor survival of newly-diagnosed MM.