Strong positive light chain immunostaining in a patient with transthyretin amyloidosis.

The two most common systemic amyloidosis types are immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) amyloidosis, in which the precursor proteins responsible for amyloidosis are light chain and transthyretin, respectively. Identification of precursor proteins is paramount to determine the type of amyloidosis, given that both amyloidosis types lack specificity in clinical presentation. Congo red staining followed by immunohistochemistry or immunofluorescence using fibril protein-specific antibodies is crucial for the diagnosis of amyloidosis. Here we describe a patient who was initially diagnosed with AL amyloidosis due to strong positive kappa light chain staining results. However, the diagnosis was corrected to hereditary ATTR amyloidosis using mass spectrometry and gene sequencing, confirming the important role of mass spectrometry in identifying the amyloid precursor protein and ruling out false-positive result from immunohistochemistry.

miR-218 contributes to drug resistance in multiple myeloma via targeting LRRC28.

Multiple myeloma (MM) is a malignant neoplasm featured by obvious drug resistance and poor prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs with crucial roles in many biological processes including cancer initiation and progression. The current study aims to investigate the pathogenic role and molecular mechanism of miRNAs in MM drug resistance. In the present study, The expression profile of miRNAs in MM samples was analyzed by microarray and real-time polymerase chain reaction. Protein expressions were detected by Western blot analysis. Cell apoptosis was detected by the Annexin V staining assay. The interaction between miRNA and the targeting mRNA was assessed using Dual luciferase reporter assay. Herein, we show that expression profile of miRNAs is deregulated in MM. miR-218, one of the most aberrational miRNAs in MM, is significantly decreased in MM cells compared to peripheral blood mononuclear cell (PBMC). Genetic manipulation reveals miR-218 control the response of MM cells to anticancer drug bortezomib (BTZ). Overexpression of miR-218 causes a significant aberrant genes expression including leucine rich repeat containing 28 (LRRC28). Mechanistic study shows that miR-218 control the drug response through mediating the expression of LRRC28 in MM cells. Overexpression of LRRC28 significantly reserves miR-218-mediated cell response to BTZ. Taken together, miR-218 is decreased in MM that contributes to BTZ resistance via targeting LRRC28, which might be used as a novel therapeutic target for multiple myeloma.

[Clinical Analysis of Cytomegalovirus Infection after Different Patterns of Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the clinical difference of cytomegalovirus (CMV) infection between HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) and haploidentical hematopoietic stem cell transplantation (hi-HSCT). METHODS: The clinical data of 83 patients who had undergone allo-HSCT were retrospectively analyzed. Out of them 50 patients underwent hi-HSCT and 33 patients received grafts from HLA-matched donors. The sera of all recipients and donors were CMV-negative before transplantation. All patients accepted myeloablative regimen without total body irradiation. PCR was performed to detect CMV in the peripheral blood twice a week after neutrophil recovery. CMV-DNA>500 copies/ml was defined as CMV viremia. RESULTS: 68 patients (81.9%) were diagnosed as CMV viremia before 100 days after transplantation. The incidence of CMV infection in hi-HSCT group was 90% and significantly higher than that in HLA-matched HSCT group (69.7%) (P < 0.05). All the patients responded well to anti-CMV therapy; however, 63 cases experienced CMV reactivation. The occurrence rate of CMV reactivation in hi-HSCT group (95.6%) was comparable to that in HLA-matched HSCT group (87.0%) (P > 0.05). Univariate analysis showed that the transplantation pattern, the recovery time of peripheral neutrophils and the occurrence of acute graft-versus-host disease (aGVHD) significantly related to the episode of CMV viremia, while the sex and age of the recipients, and the recovery time of platelets did not associate with the incidence. Further analysis found that the recovery time of neutropils and platelets in HLA-matched HSCT group were greatly shorter than those in hi-HSCT group (P < 0.05). The incidence of aGVHD was comparable between two groups however, incidence of severe aGVHD was significantly higher in hi-HSCT (P < 0.05). CONCLUSION: The hi-HSCT is more susceptible to CMV infection, which may be related to the higher incidence of severe aGVHD and the relative delay of hematopoietic reconstruction as compared with HLA-matched HSCT.

[Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy].

OBJECTIVE: To investigate the therapeutic effects of the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) or total body irradiation plus cyclophosphamide (TBI+CY) on haploidentical stem cell transplantation (HSCT) in hematologic malignancy. METHODS: The clinical outcomes of 77 HSCT recipients with hematologic malignancy from January 2001 to December 2010, including 21 AML, 33 ALL, 19 CML and 4 MDS were retrospectively evaluated. Among them, 65 patients obtained complete remission (CR) and 12 non-remission (NR) before transplantation; 39 patients received conditioning regimen with BU+CY, and 38 with TBI+CY. RESULTS: There were no statistically significant differences in hematopoietic reconstitution, disease free survival (DFS), and transplant- related mortality (TRM) between two groups. The estimated 3- years overall survival (OS) was 56.4% for BU+CY and 31.6% for TBI + CY (P=0.0283). The overall relapse rate was similar between two groups (15.4% vs 34.2%; P=0.1538). However, the accumulative probability of relapse at 1-year was significantly lower in BU+CY than that in TBI+CY group (2.56% vs 26.67%; P=0.0116). The incidence of grade II-IV graft-versus-host disease (GVHD) was similar between two regimens (20.5% in BU+CY group and 18.4% in TBI+CY group; P=0.8168). The incidence of chronic GVHD (cGVHD) was higher in the TBI+CY group than that of BU+CY group (84.6% vs 41.1%; P=0.0007). The extensive GVHD obtained the similar outcome (30.8% vs 10.5%; P=0.0416). CONCLUSION: Patients using BU+CY as conditioning regimen before transplant could obtain a better 3 year OS and lower short-term relapse rate. The TBI+CY conditioning regimen could significantly increase the incidence of cGVHD without increasing the acute GVHD. BU+CY conditioning regimen could be used for HSCT, but the attention should be paid to prevent the related hemorrhagic cystitis.