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Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.
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Objective:To investigate the expression of Toll-like receptor 8 (TLR8) in diffuse large B-cell lymphoma (DLBCL) and its correlation with clinicopathological characteristics and prognosis of patients.Methods:The data in the Oncomine database was used to analyze the difference of TLR8 mRNA expression between DLBCL tumor tissues and normal lymphocytes, and the result was verified in two independent subsets GSE 25638 and GSE 32018 of the NCBI-GEO database. The OSDLBCL online survival analysis tool was used to analyze the correlation of TLR8 mRNA relative expression level with overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Gene ontology bioprocess (GO_BP) enrichment analysis was performed by using GSEA software. The correlation of TLR8 mRNA expression with tumor immune cell infiltration degree and immune checkpoint-related molecule expression was analyzed by TIMER online tool website. A total of 53 DLBCL patients who underwent lymph node biopsy in Yancheng No. 1 People's Hospital from June 2020 to June 2021 were selected. Immunohistochemistry was used to detect the expression of TLR8 protein, and its relationship with the clinicopathological characteristics of patients was analyzed.Results:The analysis result of data from Oncomine and GEO databases showed that the relative expression levels of TLR8 mRNA in tumor tissues of patients with DLBCL or activated B cell-like DLCBL were higher than those in normal lymphocytes (all P < 0.001). The results of OSDLBCL online survival analysis indicated that the OS ( P = 0.020) and PFS ( P = 0.004) in DLBCL patients with high TLR8 mRNA expression were worse than those in patients with low TLR8 mRNA expression. The level of TLR8 was related to the abnormal function of immune response, cytokine metabolism and DNA damage monitoring; the result of TIMER online analysis showed that the expression level of TLR8 mRNA was positively related to the degree of neutrophil infiltration ( r = 0.78, P < 0.001) and the expression of immunosuppressive molecules [HAVCR2 ( r = 0.85, P < 0.001), LAG3 ( r = 0.63, P < 0.001), CD274 ( r = 0.77, P < 0.001), TIGIT ( r = 0.32, P = 0.037), and C10ORF54 ( r = 0.34, P = 0.029)]. Among 53 DLBCL patients, 29 patients (54.7%) had low expression of TLR8 protein and 24 patients (45.3%) had high expression of TLR8 protein. There were statistical differences in the expressions of TLR8 protein in DLBCL patients with different serum lactate dehydrogenase and β 2-microglobulin levels (both P < 0.05). Conclusions:TLR8 is highly expressed in DLBCL patients, and TLR8 may be a prognostic marker of DLBCL.
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Objective:To investigate the clinicopathological features, diagnosis, differential diagnosis and treatment of nodal marginal zone lymphoma (NMZL) with elevated monoclonal IgM.Methods:The clinical data of one NMZL patient with elevated monoclonal IgM treated at Yancheng No.1 People's Hospital in July 2020 were retrospectively analyzed, and the related literature was analyzed.Results:The patient was a 57-year-old female and the main clinical manifestations were fatigue and bone pain in left rib. Serum immunofixation electrophoresis showed IgM-κ type M proteinemia, bone marrow cytology showed a few plasmacytoid lymphocytes, bone marrow biopsy and immunohistochemistry showed B-cell non-Hodgkin lymphoma, bone marrow genetic testing showed MYD88 L265p and CXCR4 were both negative, postoperative pathology result of retroperitoneal lymph node biopsy was marginal zone lymphoma (mature small B type, prone to NMZL),and immunohistochemistry results: CD3, CD5, CD138, κ, λ, CD10, Cyclin D1 were negative, CD20, Pax-5, CD23 (FDC), bcl-2 were positive; Ki-67 positive index < 5%. The final diagnosis was NMZL with elevated monoclonal IgM. Partial remission was achieved after 8 cycles of reduced-dose CHOP regimen; thalidomide was used in the maintenance treatment, the disease condition was stable until August in 2021 and the follow-up was continuing.Conclusions:NMZL with elevated monoclonal IgM is relatively rare. Its diagnosis should be differentiated from Waldenstr?m macroglobulinemia and other inert B-cell lymphomas. Currently, there is no standard treatment and following the principle of individualized treatment can improve the prognosis of patients.
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Objective:To investigate the familial inheritances, clinical features, treatments and outcomes of familial Waldenstrom macroglobulinemia (WM) patients.Methods:The clinical manifestations, laboratory examinations, diagnosis and treatments, and follow-up data of 6 familial WM patients who were admitted to Yancheng No.1 People's Hospital from June 2002 to July 2019 were retrospectively analyzed, and the literature was reviewed.Results:Among 6 WM patients, 4 patients had dizziness and fatigue at the onset, 1 patient had recurrent low-grade fever and abnormal sweating as the first manifestations, 1 patient was hospitalized due to pulmonary infection, and WM was found later. Two brothers of the patients were diagnosed with WM, another 2 brothers of the patients had IgM-type monoclonal gammopathy of undetermined significance (MGUS) during the physical examination. All the 6 patients were middle-aged/elderly men, with a median age of 63 years old (51-70 years old). The median follow-up time were 71.5 months (4-217 months), and by the end of the follow-up (June 2020), 2 cases died of pulmonary infection, and 1 of them developed acute myeloid leukemia; the other 4 cases were in regular chemotherapy. Two IgM-MGUS patients were followed up without symptoms.Conclusions:WM patients have familial aggregation, and their clinical manifestations are highly heterogeneous. Patients with family history may have poor prognosis. It is necessary to strengthen the awareness of WM and family history screening.
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Objective:To investigate the expression and mechanism of hepatocyte growth factor (HGF) in multiple myeloma (MM) based on the gene information in Oncomine database.Methods:Information about HGF study in Oncomine database was collected, and the changes in HGF expression level in MM were analyzed. Genecards database was used to collect HGF gene-related proteins, and STRING software was used to draw HGF-related protein network map. The physiological process of protein function enrichment was analyzed by using DAVID online tools. The relationship between HGF expression level and survival of MM patients was analyzed by using DRUGSURV database and its online tools to explore its clinical significance.Results:A total of 445 studies on HGF in different tumors were collected in Oncomine database. In 23 studies, the difference in HGF expression level between tumor tissues and normal tissues was statistically significant ( P < 0.05), including 10 items of increased HGF expression in tumor tissues and 13 items of decreased HGF expression in tumor tissues. In 4 datasets of 3 studies on the differential expression of HGF gene in MM and normal tissues in Oncomine database, the expression of HGF in MM tissues was higher than that in normal tissues (all P < 0.05). Twenty-five HGF-related proteins were collected in Genecards database, including SDC1, YWHAG, RAF1, etc. Protein function enrichment analysis showed that these proteins were mainly enriched in the negative regulation of hydrogen peroxide-mediated programmed cell death, the regulation of synaptic plasticity, the negative regulation of death domain receptors on extrinsic apoptotic signaling pathways, etc., and they were related to PI3K-AKT and tumor-related pathways. Survival analysis based on DRUGSURV database showed that there was no significant difference in overall survival rate between MM patients with high and low HGF expression ( P > 0.05). Conclusions:HGF gene may regulate the apoptosis of MM cells through PI3K-AKT pathway and play a role in the occurrence and development of MM. HGF may be a potential marker of MM, but its value in prognostic judgment needs further research.
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Objective:To investigate the clinical features, diagnosis and treatment of lymphoplasmacytic lymphoma (LPL) with biclonal M protein.Methods:The clinical data of one LPL patient with biclonal M protein at Yancheng First People's Hospital in January 2018 was retrospectively analyzed, and relevant literature was reviewed.Results:The patient was an elderly woman with clinical manifestations of lymphadenopathy, kidney damage, anemia, and bone destruction. The diagnosis was confirmed based on lymph node biopsy, immunofixation electrophoresis, bone marrow cytology, and genetic mutation testing (MYD88 L265P mutation-positive). Partial remission was achieved after 4 courses of treatment with bortezomib-based regimen.Conclusions:Clinically, LPL with biclonal M protein shows one characteristic of M protein, and the immunoglobulin IgM and IgA biclonal LPL is even rarer. The treatment scheme based on bortezomib has a certain therapeutic effect.
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Myeloid differentiation factor 88 (MYD88) is a key linker in the Toll-like receptor (TLR) signaling pathway, which plays an important role in the progression of the tumour. Recent studies have shown that the activating mutation of MYD88 L265P has been identified in about of 90% lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia and about of 40% diffuse large B-cell lymphoma and other subtypes of B-cell proliferative neoplasms. Different types of B-cell proliferative neoplasms have their own histology, immunohistochemistry and clinical characteristics, thus, mutation rates of MYD88 L265P are different. This review discusses the latest progress of MYD88 L265P mutation in B-cell proliferative neoplasms.
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Objective To investigate the incidence of trisomy 12(+12) and 11 q23 deletion [ del ( 11q23) ] in chronic lymphocyticleukemia (CLL). Methods Fluorescein labeled DNA probe 12 and sequence specific probe ATM for 11q23 were used to perform inter-phase fluorescence in situ hybridization (I-FISH) assays in 30 patients with CLL. The results were compared with that of conventional cyto-genetic (CC) examination. Results With CC examination , only 4 cases (13.3%) were found to have chromosomal abnormalities, whereaswith I-FISH assay ,8 cases (26.7%) were found to have genomic aberrations, including trisomy 12 in 5 cases , deletion of 11q23 in 3 ca-sea. Conclusion I-FISH is a useful method for detection of genomie aberration in CLL, the significance of trisomy 12 and del (11q23) inpredicting the prognosis of B-CLL need to be investigated further.