The myeloid microenvironment of patients with multiple myeloma plays an important role in regulating the occurrence, development, invasion, secretion and angiogenesis of myeloma cells. Chemokines SDF-1 and its receptor CXCR4 form SDF1-CXCR4 biologicalaxis in bone marrow microenvironment. The role and mechanism of SDF1-CXCR4 biologicalaxis in multiple myeloma remain to be studied.

We collected 144 cases of hematology bone marrow from January 2013 to June 2017 in Southwest Medical University Affiliated Hospital and the Third People's Hospital of Chengdu, of which 104 cases were multiple myeloma patients, and 40 cases were normal as control. The relationship between SDF1-CXCR4 expression and its clinical features were analyzed. Through these analysis we tried to learn the role of SDF1-CXCR4 in the development, progression and prognosis of multiple myeloma, and hoped to provide evidence for the diagnosis and treatment of multiple myeloma.

As a result, the positive expression of SDF1 and CXCR4 in bone marrow biopsy of patients with multiple myeloma was significantly higher than that in the normal control group. More importantly, there was a positive correlation between the expression of SDF1 and CXCR4, indicating that SDF1-CXCR4 in bone marrow microenvironment plays an important role in the occurrence of multiple myeloma.

The density of microvessel density (MVD) in the myeloma was also significantly higher than that in the normal control group. The expression of SDF1-CXCR4 in the myeloma group was positively correlated with the expression of MVD. This study demonstrates that multiple myeloma cell growth and microvascular proliferation are significantly correlated in microenvironment. It is suggested that the secretion of chemokine SDF1-CXCR4 in the bone marrow microenvironment of multiple myeloma may promote microvascular proliferation and the growth of tumor cells, which may be the pathogenesis.

Multiple myeloma clinical features were analyzed according to SDF1-CXCR4 and MVD expression levels. We found that SDF1-CXCR4 and MVD expression levels were not correlated with gender, age and immunoglobulin typing, but were significantly correlated with multiple myeloma staging in bone marrow tissue of MM patients. But we found that in the later stage of SDF1, the expression level of SDF1、CXCR4 and MVD is higher. This finding further indicates that chemokine SDF1-CXCR4 secretion and microvascular proliferation play important roles in progression of multiple myeloma.

The Kplan-Meier analysis on overall survival (OS) and progression-free survival (PFS) was performed according to the levels of SDF1-CXCR4 and MVD expression in multiple myeloma. We discovered that the OS rate and PFS rate were lower in the patients with higher expression of SDF1, CXCR4 and MVD , which indicates that chemokine SDF1-CXCR4 secretion and microvascular proliferation also play important roles in prognosis of multiple myeloma.

Our findings reveal that chemokine SDF1-CXCR4 secretion and microvascular hyperplasia in bone marrow microenvironment are essential in the occurrence, development and prognosis of multiple myeloma. The higher secretion of chemokine SDF1-CXCR4 suggests the worse progression and poor prognosis. Chemokine SDF1-CXCR4 is expected to become a new target for MM treatment.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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