Wenming Chen

Retrospective analysis of genetic abnormalities and survival in 131 patients with multiple myeloma.

Genetic abnormalities in patients with multiple myeloma (MM) are important risk factors in terms of prognosis. In the present study, the prognostic value of several common MM genetic abnormalities was investigated. Interphase fluorescence in situ hybridization (iFISH) was used to detect genetic abnormalities, including 1q21 gain, t(4;14), t(11;14), t(14;16) and 17p13 deletion in 131 patients. A total of 46.6% patients were detected with one or more abnormalities using iFISH analysis. The 1q21 gain, t(4;14), t(11;14), t(14;16) and 17p13 deletion abnormalities were detected in 42.5, 6.9, 17.5, 0.8 and 10.7% of patients, respectively. Patients with t(4;14) commonly exhibited lower levels of albumin and hemoglobin. The progression-free survival (PFS) and overall survival times of iFISH-positive patients (particularly patients with two or more iFISH abnormalities) were significantly shorter than those of the patients without detectable abnormalities. The 1q21 gain and 17p13 deletion were also adverse prognostic factors for MM. Bortezomib-based therapies improved the PFS times in the patients with unfavorable iFISH abnormalities. These findings demonstrate that patients with two or more iFISH abnormalities, a gain of the 1q21 region or a 17p13 deletion were more likely to have a poor prognosis; however, bortezomib treatment improved the outcome for MM patients with unfavorable iFISH abnormalities.

Toll-Like Receptor 4 Is Required for the Cytotoxicity of Cytokine-Induced Killer Cells

Cytokine-induced killer (CIK) cells are heterogeneous effector T cells with diverse T-cell receptor specificities with non-major histocompatibility complex-restricted cytolytic activities against tumor cells and are considered a promising therapeutic approach against hematologic malignancy. Recently, it has been reported that IL-15-activated CIK cells are superior to cells generated according to the standard protocol; however, the underlying mechanism remains to be elucidated. In the present study, we found that in IL-15-stimulated CIK cells, Toll-like receptor 4 (TLR4) expression was upregulated. Upon knockdown of TLR4, the cytolytic activity was considerably compromised. Re-expression of TLR4 in CIK cells restored their function, confirming the essential role of TLR4 in CIK cell cytotoxicity. Collectively, our study demonstrated that TLR4 was essential for the cytotoxicity of CIK cells against tumor cells, which might provide a novel approach to promote the therapeutic efficacy of CIK cells against hematologic malignancy.

Retrospective analysis of 264 multiple myeloma patients

Multiple myeloma (MM) is the second most common hematological malignancy in China. However, there are only a small number of large cohort studies demonstrating the clinical features of newly diagnosed MM. In the present study, 264 newly diagnosed MM patients from the Beijing Chaoyang Hospital were retrospectively analyzed. The median patient age was 59 years (range, 28–84) and the most common monoclonal protein (42%) was the IgG subtype. Of the 49 patients detected by FISH, 10.2, 2.0 and 12.2% demonstrated del(17p), t(14;16) and t(4;14), respectively. In total, 228 (86%) patients achieved either a complete response (CR), a very good partial response (VGPR) or a partial response (PR). The overall response rate (ORR) in non-autologous stem cell transplantation (non-ASCT) patients was 83.0%, with 48 (18.2%), 7 (2.7%) and 121 (45.8%) patients achieving CR, VGPR and PR, respectively. ASCT patients achieved at least a PR prior to ASCT, and ASCT was not able to increase the ORR (P=0.55). Non-ASCT patients who received bortezomib-based regimens demonstrated an improved ORR compared with those who received regimens that did not contain bortezomib (92.3% vs. 75.8%; P<0.05). With a median follow-up time of 20 months, the estimated median progression-free survival (PFS) and overall survival (OS) times were 27.6 and 61.0 months, respectively. The OS time of patients with high-risk cytogenetic abnormality, del(17p), t(14;16) and t(4;14), was shorter compared with that of other patients (30.2 months vs. not reached, P=0.029). Patients who achieved a CR/VGPR in the ASCT group demonstrated a greater OS time compared with non-ASCT patients (P=0.031). Relapsed patients who received bortezomib-based regimens did not demonstrate a longer survival time post-relapse compared with those who received non-bortezomib-based regimens (26.5 months vs. 10.5 months; P=0.271). The current study presented the clinical characteristics of MM patients who were initially treated at the Beijing Chaoyang Hospital. Bortezomib-based regimens and ASCT were able to improve the OS of MM patients.

Effects and mechanism of arsenic trioxide in combination with rmhTRAIL in multiple myeloma

The anti-tumor potential of arsenic trioxide (ATO) and recombinant mutant human TRAIL (rmhTRAIL) has been confirmed in various kinds of tumors. However, the effects and mechanism of the two drugs in combination in multiple myeloma (MM) have not been established. In this study, we evaluated the proliferation inhibition and apoptosis induction effects of ATO and rmhTRAIL as single agents and in combination on the MM cell lines RPMI8226 and U266. Then, we used high-performance liquid chromatography and mass spectrometry to find differentially expressed proteins before and after drug treatment and to analyze the mechanism underlying the effect of ATO and rmhTRAIL on MM cells. Results indicated that ATO and rmhTRAIL had synergistic or additive effects on proliferation inhibition and apoptosis induction in MM cells, and the mechanism underlying the two-drug combination might involve regulation of the expression of several proteins affected by ATO and rmhTRAIL. Our study provides evidence of a potential new combination treatment strategy for MM.

Mixed lineage leukemia‑septin 5 fusion transcript in de novo adult acute myeloid leukemia with t(11;22)(q23;q11.2): A case report

The current report presents a case of de novo acute myeloid leukemia (AML) in a 32-year-old male. Cytogenetic analysis showed that the karyotype of the bone marrow cells was as follows: 46,XY,t(11;22)(q23;q11.2)[13]/46,X,−Y,+10,t(11;22)(q23;q11.2)[7]/47,XY,+10,t(11;22)(q23;q11.2)[1]/46,XY[1]. Fluorescence in situ hybridization analysis using a mixed lineage leukemia (MLL)-specific probe showed a split in the MLL gene. Reverse transcription polymerase chain reaction (PCR) analysis demonstrated an MLL-septin 5 (SEPT5) fusion transcript in the patient. Nucleotide sequencing analysis of the PCR product confirmed the fusion between the MLL exon 9 and SEPT5 exon 3, and the product was 521 bp in length. The present study reviewed the clinical and molecular features of the AML with an MLL-SEPT5 fusion gene.

Multiple myeloma with extramedullary plasmacytoma invading the skin and eyeballs following autologous stem cell transplantation: A case report

In this study, the case of a 60-year-old female patient who presented with a subcutaneous mass in the lower right limb is described. The mass was confirmed as a plasmacytoma. The patient was diagnosed with multiple myeloma (MM) λ type stage III international stage system (ISS) and received three cycles of a therapeutic PDT regimen (bortezomib, dexamethasone and thalidomide) and complete remission was achieved. Following a further two cycles of the PDT regimen, the patient proceeded to received a high-dose cyclophosphamide regimen combined with granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization. Fourteen months later, the patient received a high-dose therapy supported by autologous stem cell transplantation (auto-SCT). After six months, a subcutaneous mass was identified in the left side of the patient’s neck and the mass gradually increased in size. The patient exhibited exophthalmos and loss of sight one month later. The masses in the neck and right eyelid of the patient were diagnosed as plasmacytomas. These results, combined with the results of bone marrow (BM) aspiration and protein electrophoresis with immunofixation electrophoresis revealed that the disease had relapsed. The patient received two cycles of a therapeutic CPADT regimen (cyclophosphamide, bortezomib, pharmorubicin, dexamethasone and thalidomide). The patient subsequently achieved complete remission again. The patient refused to continue receiving bortezomib and pharmorubicin for therapy and instead received four cycles of the therapeutic CTD regimen (cyclophosphamide, dexamethasone and thalidomide). Subsequently the patient received local radiotherapy for the masses in the eyes and neck. The patient remained stable after treatment following the initial relapse with a progression-free survival (PFS) time of eight months.

A Report of 134 Newly Diagnosed Multiple Myeloma Patients with Renal Impairment

To analyze the effects of bortezomib on the prognosis of the newly diagnosed multiple myeloma patients with renal impairment, we assessed the outcomes of 134 multiple myeloma patients with renal impairment (serum creatinine ≥178 μmol/l) who were treated at Beijing Chaoyang Hospital. The patients were divided into two groups: bortezomib (n = 83) and nonbortezomib (n = 51). The overall response rate of the bortezomib group was higher than that of the nonbortezomib group. There was no significant difference in the time to restore renal function, but the complete renal response ratio was significantly higher in the bortezomib group. The 2-year overall survival (OS) rate of the bortezomib group was significantly greater than the nonbortezomib group, as was the 3-year OS rate. Kaplan-Meier analysis revealed significantly better survival for the bortezomib group. The main side effects in the bortezomib group were thrombocytopenia, peripheral neuropathy, infection, and herpes zoster, and there was a low incidence of grades 3 and 4 adverse events. Our findings indicate that bortezomib-based combination chemotherapy can improve the prognosis of the newly diagnosed multiple myeloma patients with renal impairment and should be considered as a first-line therapy.

Significance of p85 expression as a prognostic factor for patients with breast cancer

p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI3K), functions in the pathogenesis and progression of human breast cancers. Previous studies have observed that p85 isoforms may correlate with cancer cell proliferation. In the present study, immunohistochemical staining of p85 was performed in 126 primary breast cancers. The association between the expression levels of p85 with clinicopathological variables, subtypes and prognosis was studied. The breast cancer specimens were divided into three subgroups according to the expression levels of p85 protein. High p85 protein expression was significantly correlated with tumor grade, vascular invasion and recurrence and/or metastasis (P<0.05). Increased p85 protein expression was associated with the human epidermal growth factor receptor 2-positive and triple-negative breast cancers (P=0.008). Patients with higher p85 protein expression levels showed shorter disease-free survival and overall survival times as compared with those with lower expression levels of p85 (P<0.001). Cox proportional-hazards analysis showed that p85 protein expression was not an independent prognostic factor. Further large-scale studies are required to evaluate the significance of p85 protein expression as a prognostic marker for breast cancer.

Comparable outcome of stem cell transplant versus bortezomib-based consolidation in myeloma patients after major response to induction

Abstract High-dose therapy with autologous stem cell transplant (ASCT) has been established as standard treatment for eligible patients with myeloma. However, whether this approach is still beneficial with new therapy is yet to be determined. Consolidation of effective therapy may be an alternative to ASCT following major response to initial induction. This retrospective case-series analysis included a total of 48 patients with newly diagnosed myeloma. All these patients achieved complete response or very good partial response to bortezomib-based induction and were eligible for ASCT; 24 of these patients proceeded with ASCT, and other 24 patients opted out of ASCT and received two additional cycles of bortezomib therapy as consolidation. With a median follow-up of 28.5 months in ASCT group and 29 months in non-ASCT group, no significant difference was seen in progression-free survival, 39 versus 32 months, P = 0.82. Median overall survival had not been reached, and the estimated 3-year overall survival rates were 87.5 and 67.5% in ASCT and non-ASCT, respectively, P = 0.97. This study provides an initial assessment of survival outcome of ASCT in comparison with non-ASCT consolidation. The additional study is required to establish the efficacy of non-ASCT consolidation.

Down‑regulated G protein‑coupled receptor kinase 6 leads to apoptosis in multiple myeloma MM1R cells

G protein-coupled receptor kinase 6 (GRK6) is highly expressed in multiple myeloma (MM) cell lines, but absent or only weakly expressed in most primary human somatic cells. In the present study, GRK6 expression was assessed in MM patients and healthy individuals by quantitative polymerase chain reaction. Flow cytometry were performed to measure the apoptosis of lentivial-transfected MM1R cells. Western blot analysis was performed to assess the apoptosis and signal transducer and activator of transcription 3 pathway-related factors. The results demonstrated that GRK6 was differentially expressed in individuals who suffered from MM and healthy individuals. Previous studies have shown that downregulating GRK6 has anti-cancer effects in the MM cell line, MM1R. The present study demonstrated that RNA interference-mediated GRK6 knockdown promoted apoptosis in the MM1R cell line. Therefore, we hypothesized that GRK6 plays a significant role in determining the course of MM.