Explore The Pathogenesis Of POEMS Syndrome

BackgroundPOEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. The pathogenesis of POEMS syndrome is poorly understood. Vascular Endothelial Growth Factor (VEGF) is the most important cytokine in this disorder. Few researches have explored the cytogenetic characters of POEMS syndrome, as well as its pathogenesis of bone disease.Object1. Purify CD138+plasma cells form bone marrow aspirates of POEMS synerome patient, detect the cytogenetic aberrations by iFISH.2. Measure the level of bone turnover markers in POEMS synerome patients, as well as several key cytokines in bone metabolism, explore the potential pathogenesis of bone disease in POEMS syndrome.3. Measure the serum VEGF level in POEMS syndrome and peripheral neuropathy patients, explore its value in differential diagnosis.MethodCollect bone marrow aspirates of POEMS syndrome patients, purify plasma cells by CD138immunomagnetic beads, detect their cytogenetic aberrations by iFISH, and compare the result with other plasma cell dyscrasia. CTX, P1NP level were measured by an electrochemiluminescence system. DKK-1, OPG, sRANKL level were measured using their ELISA kit respectively. Compare levels of these cytokines among patients with different bone disease manifestation in X ray. Collect clinical data, comepare VEGF levels between POEMS syndrome and peripheral neuropathy patients.Result1. Detect cytogenetic aberrations in20POEMS syndrome patients.13/20(65%) patients were found to bear cytogenetic aberrations commonly seen in Multiple Myeloma(MM).14q32(IGH) aberration was observed in9/20(45%) cases, t(4;14)(4p16;14q32) was observed in4/20(15%) cases, t(11;14)(11q13;14q32) was observed in5/20(25%)cases.5patients had del(13q14),4patiens had1q21(CEP1) amplification.17pl3(TP53) aberration and t(14;16)(14q32;16q23) were not observed.2. The CTX and P1NP levels in POEMS syndrome patiens were both significantly higher than those of the health control (CTX:0.9386±0.6955vs0.5696±0.0604pg/mL,P=0.002, P1NP:172.014±139.271vs52.263±6.555pg/mL, P<0.001。3. The DKK-1level in patiens with bone diseases (including osteosclerosis and lytic bone lesions) was significantly higher than that of other patiens(1661.71±181.45vs914.12±175.85pg/mL,P=0.018), yet its level has no statistical difference between patients with osteosclerosis and lytic bone lesions. Patients with osteosclerosis leisions had a significantly lower level of RANKL than patiens without bone diseases (5.877±0.298vs8.286±1.229pmol/mL,P=0.017), while the level in patiens without bone diseases was significantly lower than patiens with lytic bone lesions (8.286±1.229vs10.900±1.184pg/mL,P=0.003) Patients with osteosclerosis leisions had a significantly lower RANKL/OPG ratio than other patients (0.0611±0.0059vs0.1346±0.0148pg/mL, P<0.001), yet the ratio has no statistical difference between patiens with lytic bone lesions and without bone diseases.4. There was a positive relationship between levels of serum VEGF and P1NP (r=0.315, P=0.020) in POEMS syndrome.5. Level of serum VEGF in POEMS syndrome patients (n=60,2407.6±259.2pg/ml) was significantly higher than that in normal control (n=10,425.3±100pg/mL, P<0.001), MM patients(n=15,412.0±100.7pg/mL, P<0.001), peripheral neuropathy patients (n=27,1439.2+148.1pg/mL,P=0.043)6. Among POEMS syndrome patiens, those with Castleman’s disease bore a significantly lower level of VEGF than other patients (904.3±195.3vs2056.2±281.4pg/mL,P=0.009), those with abnormal urinalysis bore a significantly higher level of VEGF than other patients (3694.3±719.1vs1393.7±202.5pg/mL, P=0.043)Conclusion1. Most POEMS syndrome patients bear one or more than one kind of cytogenetic aberrations, including13q14(RB-1) deletion,1q21(CEP1) amplification, t(11;14)(11q13;14q32) and t(4;14)(4p16;14q32). 2. Most POEMS syndrome patients have bone metabolism disorder, it might be seen as one of the minor criteria in diagnosis of POEMS syndrome.3. Measurement of VEGF level helps to differentiate among POEMS syndrome, MM, peripheral neuropathy.