应用MALDI-TOF质谱技术检测多发性骨髓瘤Jak2基因单核苷酸多态性

本研究探讨基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOFMS)检测多发性骨髓瘤(MM)jak2基因的单核苷酸多态性(SNP)的实用性。用PCR扩增出含jak2基因2个SNP(C428T和C643T)位点的DNA片段作为模板,产物纯化后利用MALDI-TOFMS检测5例MM和5例健康对照者样本的jak2基因多态性。结果表明:C428T和C643T位点基因型在多发性骨髓瘤病例与健康对照组的分布无差异,均为T/T纯合子。结论:本实验建立的基于MALDI-TOFMS与引物延伸技术检测jak2基因多态性的方法是一个快速、准确和可靠的检测方法。

Clinical Features of Renal Insufficiency due to Multiple Myeloma and Related Risk Factors

Objective: To study clinical features of the patients with multiple myeloma(MM) accompanied by renal insufficiency and investigate the related risk factors of renalimpairment. Methods: A control study of clinical characteristics was performed between 91 patientswith renal insufficiency due to MM and 165 patients with normal renal function in MM during the sameperiod. The data were statistically analyzed by chi-square test and logistic regression analysis.Results: Renal insufficiency was the initial presentation in 48 (52.7%) of the 91 patients, and 30(62.5%) of the 48 patients were misdiagnosed. The prognosis of group with renal insufficiency wassignificantly poorer than that of group with normal renal function: mortality in 3 months, 3months-1 year was 26/91 vs 14/165 (P 【 0.0001), 14/91 vs 12/165 (P 【 0.05) respectively, andpatients survived 】 1 year was 18/91 vs 95/165 (P 【 0.0001). The incidence of hypercalcemia,hyperuricemic, severe anemia, high serum M-protein concentration and lytic bone lesions weresignificantly higher in renal insufficiency group than those in control group (P 【 0.05). Logisticregression analysis identified 5 risk factors of renal impairment, including, severe anemia(Exp(β)=13.819, P 【 0.0001), use of nephrotoxic drugs (Exp(β)=6.217, P = 0.001), high serumM-protein concentration (Exp(β) = 5.026, P = 0.001), male (Exp(β)=3.745, P=0.006), andhypercalcemia (Exp(β)=3A72, P=0.006), but age, serum density of uric acid, type of serum M-protein,and Bence Jones proteinuria were not significantly associated with renal insufficiency. Conclusion:Renal insufficiency was a common early complication of MM, which often resulted in misdiagnosis.The status of these patients tended to be very bad, with many other complications, when MM wasdiagnosed, so their prognosis was poor. The occurrence of renal insufficiency in patients with MMand hypercalcemia, severe anemia, high serum M-protein concentration, especially use of nephrotoxicdrugs should be alert.

Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate:a case report

Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co- existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.

Concomitant Chronic Lymphocytic Leukemia and Multiple Myeloma: Proof of Common Clonal Origin

We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.

Nodular liver lesions involving multiple myeloma: A case report and literature review

We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus （HCV）. With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.

Triptolide and management of systemic malignancies besides pancreatic carcinomas

The recent article by Zhou et al was highly interesting and thought provoking. The authors have clearly shown that triptolide administration is associated with upregulation of the Bax gene, resulting in an attenuating effect on cell growth in gastrointestinal malignancies such as pancreatic carcinomas. The article by Zhou et al is all the more important because it highlights the rapidly increasing role of triplodide in the management of systemic malignancies. For instance, triptolide acts on the PI3K/Akt/NF-κB pathway, thereby enhancing apoptosis secondary to the administration of bortezomib in multiple myeloma cells. Similar synergisms are seen when triptolide is administered along with 5-fluoruracil for the management of colonic carcinomas. Similarly, triptolide causes down-regulation of the Bcl-2 gene, resulting in control of cell growth in tumors, such as glioblastoma multiformes.

Hepatic failure caused by plasma cell infiltration in multiple myeloma

Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma （MM）, it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stageⅡB. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction. Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

Why bortezomib cannot go with ‘green'?

Eat more‘green’or eat‘five a day’is one of the most important healthy lifestyle behaviours in the 21 century.Aiming to fight cancer effectively,more than half patients use vitamins or herbs concurrently with conventional anticancer treatment.Flavonoids or polyphenols existing in vegetables,fruits and green tea are common plant pigments with antioxidant properties and considered acting as cancer preventing or anti-cancer agents.Recently it was found that some flavonoids and vitamin C in diet or supplements have antagonistic effect with the anti-cancer drug bortezomib.Bortezomib is a specific inhibitor for proteasome and is currently used for treatment of relapsed and refractory multiple myeloma.Despite its successful rates in treating multiple myeloma and other solid tumors,it is unable to kill leukemic cells in the blood.It was recently revealed that some flavonoids and vitamin C present in green leaves and green teas in the blood can neutralize bortezomib by directly interaction between two chemicals.Here we summarize why dietary flavonoids should be avoided in patients who take bortezomib as chemotherapeutic drug.

The value of radionuclide bone imaging on monitoring chemotherapeutic effects of multiple myeloma

Objective： To investigate the value of radionuclide whole-body bone imaging on monitoring chemotherapeutic ~ffects for multiple myeloma （MM）. Methods： Sixty patients were included. Twenty nine cases received CTD （thalidomide 100-200 rag/d; cyclophosphamide 200-300 mg/m2od, 1-4 days, every 4 weeks; and dexamethasone 20-40 rag/d, 1-4 days, every 4 weeks）; Thirty cases received VAD （vincristine 0.4 mg/d, 1-4 days, every 4 weeks; adriamycin 10 mg/d, 1-4 days, every 4 weeks; dexamethasone 40 rag/d, 1-4 days, every 4 weeks）. Radionuclide bone imagings were performed in all patients before chemotherapy, six months, twelve months and eighteen months after chemotherapy. The correlation of chemothera- peutic effects between CTD and VAD were analyzed. Results： One hundred and seventy nine bone lesions were visualized by bone scintigraphy before CTD treatment. Eighteen months after CTD chemotherapy, it was observed by bone scintigraphy that 39/179 （21.78%） lesions disappeared, 112/179 （62.57%） improved, and 281179 （15.64%） had no change. One hundred and ninety one bone lesions were showed by bone imaging before VAD treatment, 361191 （18.84%） lesions disappeared, eighteen months after chemotherapy, 103/191 （53.92%） improved, and 52/191 （27.22%） had no change. The significant dif- ference was observed in locations of MM induced bone lesions treated with CTD （H = 8.23, P 〈 0.05） and VAD （H = 11.18, P 〈 0.05）. A significant chemotherapeutic sensitivity in detecting MM induced lesions in ribs was found compared with other bone lesions. The chemotherapeutic effect of CTD was statistically significant than that of VAD （U = 2.17, P 〈 0.05）. Conclusion： Radionuclide whole-body bone imaging has great value in monitoring chemotherapeutic effects for MM.

Resolution of pleural effusion in a IgD multiple myeloma after chemotherapy based on liposomal doxorubicin

IgD myelomas account for only 2% of all myelomas. This kind of hematological malignancy is severe and carries a bleak prognosis. Pleural effusion is very rare in multiple myeloma. We reported a case in which pleural effusion appeared at the end of the illness of IgD myeloma and treated with liposomal doxorubicin.

Therapy of Multiple Myeloma

Summary Multiple Myeloma(MM)is characterised by the accumulation of malignant plasma cells in the bone marrow producing a monoclonal immunoglobulin.The standard conventional therapy is the combination of melphalan and prednisone resulting in a response rate of 40%-60%and in a median survival time of approximately 3 years.In order to improve the therapeutic efficacy various combination regimens have been tested.Most randomized trials have frailed to show a significant improvement in survival time when combination chemotherapy is used instead of melphalan with or without prednisone.The benefit of maintenance therapy with interferon-alpha has been demonstrated.The toxicity of interferon-alpha,which may reduce the quality of life,should be considered.Recently,myeloma-treatment has been modified.High-dose chemotherapy accompanied by hematopoietic stem-cell support via autologous transplant is recommended up to the age of 65-70 years.First results from a French study comparing single versus double autologous transplantation have shown a benefit in terms of event-free survival for the sequential approach.Vaccinations as an adoptive immuntherapy to treat minimal residual disease are under way.The mortality rale of allogeneic transplantation of hematopoietic stem cells has been reduced in the last 5 years.The use of reduced conditioning regimens or the partial depletion of T cells in peripheral blood stem cell transplants in an effort to decrease transplant related mortality are promising approaches.Thalid-omide and its derivates are a new class of agents with independent anti-tumour activity in MM.Encouraging results with this antian-giogenic therapy in phase II trials have been reported.Supportive therapies,such as the treatment of anaemia with erythropoietin,the management of renal failure and the use of bisphosphonates,improve the life quality of MM patients.

Low Grade Fibromyxoid Sarcomas and Multiple Myeloma in the Same Patient： One Case Report and Literature Review

IntroductionMultiple myeloma （MM） is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein（M-protein） in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; and renal insuf.ciency or failure.According to the results of immunoelectrophoresis, patients are separated to Ig type （IgG, IgA, IgD, IgE and IgM）; light chain; nonsecretory.

Renal Extramedullary Plasmacytoma--One Case Report

Extramedullary plasmacytoma （EMP） is rare in multiple myeloma, especially kidneys are involved. We report one case, including diagnosis and treatment. The purpose of this paper is to provide an attention on the extramedullary plasmacytoma disease, reducing the misdiagnose with this disease.

Arsenic trioxide potentiates the effect of bortezomib on the proliferation and apoptosis of multiple myeloma cell line KM_3

Objective： The aim of our study was to investigate the effect of bortezornib in combination with arsenic trioxide （As2O3） on the proliferation and apoptosis in the human multiple rnyelorna cell line KM3. Methods： KM3 cells were cultured with different concentrations of bortezomib, As2O3 alone or in combination for different times. Cell proliferation was analyzed by MTT assay, and the ICso was calculated. Cell morphology was observed under the light microscope （using Wright-Giernsa stain） and electric microscope. Agarose gel electrophoresis was used to evaluate DNA content. Flow cytornetry was used to examine Annexin V-FITC/PI stain and mitochondrial transmembrane electric potential （△ψm）. Results： Bortezornib and As2O3 alone both inhibited KM3 cell proliferation in a time and dose dependent manner, with the IC50 were 0.27, 3.10 μmol/L, respectively; the inhibiting rate on KM3 cells of bortezornib plus As2O3 was significantly higher than bortezornib alone （18.22± 1.04）% vs. （13.18± 1.29）%, P 〈 0.05; A series of typical morphological features of apoptosis and a typical DNA ladder were observed in KM3 cell treated with 0.25 μm/L bortezornib for 48 h, which showed increased Annexin V positivity and decreased △ψm. The apoptosis rate induced by bortezornib plus As2O3 was also significantly than that of induced by bortezornib alone. Conclusion： Bortezornib could inhibit the proliferation while induce apoptosis of KM3 cells which may be through decreased △ψm. Bortezornib had enhanced inhibitory effect with As2O3 on the growth of KM3 cell （P 〈 0.05）. As2O3 enhances the apoptosis effects of bortezomib on KM3 cell.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors(u PAR) in bone marrow fluid and bone marrow tissue from multiple myeloma(MM) patients and assess association of u PAR level with prognosis of MM.Methods u PAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow(control) were examined by ELISA.Furthermore,u PAR expression in bone marrow tissue was investigated by RT-PCR and Western blot,respectively.The distribution of u PAR in MM cells was examined using immunofluorescence staining.The pathological changes in different stages of MM patients were studied by HE staining.Results u PAR level in bone marrow fluid of MM patients(1.52±0.32 μg/ml) was found to be higher than that in the control group(0.98±0.15 μg/ml).Interestingly,u PAR protein(0.686±0.075 vs.0.372±0.043,P<0.05) and m RNA(2.51±0.46 vs.4.46±1.15,P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage.The expression of u PAR in MM bone marrow was confirmed by immunofluorescence staining.Moreover,HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma.Conclusion Our study reveals that u PAR expression is positively correlated with the development and progress of MM.

Altered gene expression reveals molecular mechanisms underlying oridonin-induced apoptosis of multiple myeloma LP-1 cells

Objective： To investigate the effect of oridonin on proliferation and invasion of human multiple myeloma LP-1 ceils and the underlying mechanism. Methods： LP-1 cells in culture medium in vitro were treated with oridonin at the different concentration Cell proliferation was measured by Microwave Theory and Techniques （MTT） assay and cell apoptotic rate was detected by flow cytometry. Morphology of cell apoptosis was observed by transmission electron microscope. Expressions of Bax, Bcl-2, Caspase-3, NFqcB as well as I-~B mRNA were detected by real-time PCR. Results： The MTT assays and flow cytometry revealed that oridonin could inhibit the growth of LP-1 cells and cause apoptosis significantly; the suppression was both in time- and dose-dependent manner. Marked morphological changes of cell apoptosis were found under a transmission electron microscope after the cells were treated with oridonin at 25 ~rnol/L for 24 h. Along with the apoptotic process, Bcl-2, Caspase-3,NF-r,.B gene expressions were down-regulated （P〈0.05）. On the contrast, the Bax and I-~zB gene expressions were up-regulated （P〈0.05）. Conclusion： Oridonin could inhibit the proliferation of LP-1 cells via inducing apoptosis. We concluded that oridonin induces apoptosis in LP-1 cells via activation of caspase-3 as well as down-regulation of Bcl-2 and up-regulation of Bax expression. The results suggested that oridonin could induce apoptosis of LP-1 cells through mitochondria- and caspase3-dependent pathways. Meanwhile, the inhibition of NF-r,_B and the activation of I-~B indicate pro-apoptotic stimuli. In one word, oridonin might be an important potential anti-myeloma reagent.

Allogeneic Immunotherapy for Relapsed Multiple Myeloma：Role of Matched Unrelated Donors

Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation, such as older and heavily pretreated patients. In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation, we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality. With a short median follow-up of 225 days, disease control was achieved only for patients responding to conventional treatment prior to allografting. Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.

Dexamethasone plus lenalidomide in treatment of multiple myeloma

Combination of lenalidomide with dexamethasone （LD） is of high effectiveness for treatment of multiple myeloma （MM）, resulting in an improved overall survival, response rate, and time to progression in relapsed or refractory MM. Adverse events, especially venous thromboembolism, were generally well tolerated. In addition, lenalidomide plus dexamethasone is a potential therapy in maintenance of myeloma.

An Open-Label Study of Pegylated Liposomal Doxorubicin,Vincristine, and Reduced-Dose Dexamethasone Combination Therapy in Newly Diagnosed Multiple Myeloma Patients in the Chinese Population

OBJECTIVE Though doxorubicin is highly active in the treatment of multiple myeloma, its toxicity profile limits its therapeutic index. We performed this study to evaluate the efficacy and liposomal doxorubicin （PLD, Ca of pegylated , vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma （MM） patients in a Chinese population. METHODS This was an open-label, single-arm study in which newly diagnosed patients with MM received PLD 40 mg/m2 intravenously on Day 1, vincristine 1.4 mg/m2 intravenously （maximum 2 rag） on Day 1, and 40 mg of dexamethasone （intravenously or orally） from Day 1 to Day 4. Treatment was repeated every 28 days for at least 4 cycles. RESULTS In the intent-to-treat （ITT） analysis, the overall response rate was 68.29%, and the complete remission rate was 10.98%. The incidence of all adverse events was 46.34%. The most common non-hematologic toxicities were palmar-plantar erythrodysesthesia （13.4%） and stomatitis （6.1%）. CONCLUSION PLD, vincristine, and a reduceddose dexamethasone combination （DVd） is an effective and safe regimen in newly diagnosed MM patients in a Chinese population.

Renal impairment in multiple myelomas

Objective: The aim of the study was to investigate the clinic manifestation, diagnosis and treatment on multiple myeloma (MM) with the onset of renal impairment. Methods: The 27 cases of multiple myeloma with the onset of renal impair-ment were collected in Department of Nephrology, Wuhan General Hospital of Guangzhou Command, China, from January 2007 to January 2011. All cases were divided into the groups with renal dysfunction (n = 16) and normal renal function (n = 11). The clinic manifestations, treatments and prognosis of all patients were analyzed. Results: Of all the patients in normal renal function group, 5 suffered nephrotic syndrome, 4 had abnormal results of routine urinalysis (hematuria or proteinuria) which were not caused by nephrotic syndrome, and 1 suffered urinary tract infection. Five pathological specimens of renal biopsy revealed that light chain protein, immunoglobulin and complement C3 were deposited mainly in the glomerular base-ment membrane and mesangia, tubular basement membrane and arteriolar walls. Two pathological specimens were proved to be renal amyloidosis. Patients with renal dysfunction had poorer prognosis, severer anemia, higher values of serum lactate dehydrogenase (LDH) and β2-microglobulin (β2-MG), worse responses to chemotherapy. Of 16 patients with renal dysfunc-tion, 14 (87.5%) were stage III, which were significantly higher than that in the group of normal renal function [63.6% (7/11)]. Of 16 cases with renal dysfunction, 9 were treated with blood purification, and 5 of 9 cases were treated with plasma exchange. Conclusion: Multiple myeloma with the onset of renal impairment was easily misdiagnosed. Hemodialysis concomitant with chemotherapy could contribute to recovery of renal function.