ABSTRACT
BACKGROUND: Sequential monitoring of Wilms' tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. METHODS: Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan-Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. RESULTS: Of the 151 consecutive patients included, the median age was 10 years (range, 1-17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25-6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. CONCLUSIONS: Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.
Subject(s)
Biomarkers, Tumor/metabolism , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Neoplasm Recurrence, Local/epidemiology , WT1 Proteins/metabolism , Adolescent , Biomarkers, Tumor/analysis , Bone Marrow/pathology , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Incidence , Infant , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Neoplasm Recurrence, Local/pathology , Neoplasm, Residual , Prognosis , Risk Assessment/methods , Transplantation, Homologous , WT1 Proteins/analysisABSTRACT
OBJECTIVE: To explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease. METHODS: Peripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot. RESULTS: FCM showed only 1 case with clonal TCRVß in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot. CONCLUSION: Detecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.
Subject(s)
Clone Cells , Epstein-Barr Virus Infections/complications , Lymphocytes/physiology , Lymphoproliferative Disorders/virology , Adult , Blotting, Southern , Cell Proliferation , Herpesvirus 4, Human , Humans , Infectious MononucleosisABSTRACT
BACKGROUND AND AIM: Dicer is one of the most important components in microRNA biogenesis. Although studies have revealed the aberrantly expression of Dicer in types of cancer, the results were greatly controversial. Here we aimed to study the expression of Dicer in gastric cancer (GC) and further explored the possible roles of Dicer in cancer progression. METHODS: The alteration of Dicer-expression in GC and its clinical significance was retrospectively studied with immunohistochemical analyses on 377 cases of cancer tissues using tissue microarray (TMA). Dicer mRNA and protein levels were also examined in 8 paired of GC tissues and non-neoplastic surrounding gastric epithelium with real time RT-PCR and western blot. RESULTS: We found that Dicer was reduced in GC tissues in both mRNA and protein levels. Moreover, down-regulation of Dicer was correlated highly with tumor differentiation (P<0.05) and lymph node invasion (P<0.05) in GC tissues, which suggested an essential role of Dicer in cancer invasion. CONCLUSIONS: Considering that Dicer might be closely related to progression of GC, we proposed that Dicer might offer a promising target for prevention of metastatic progression in GC.