Transformed essential thrombocytosis with a JAK2 V617F mutation relapsing as JAK2 mutation-negative leukaemia after allogeneic stem cell transplantation.
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Cell Transformation, Neoplastic↗
Biomedical subjects
R Liang
Publications and source records attributed to R Liang.
Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia.
Dysregulation of apoptosis, and thus the p14/DAP kinase/HDM2/p53/Apaf-1 pathway, is potentially important in carcinogenesis. Chronic lymphocytic leukemia (CLL), uncommon in the Chinese, is a disease characterized by impaired apoptosis, of the neoplastic lymphocytes. Hypermethylation of p14, DAP kinase and Apaf-1 was studied by methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) alleles in 50 diagnostic marrow samples from patients with CLL. Chinese CLL patients had an indolent course similar to Caucasians with median overall survival (OS) of 96 months, which was adversely affected by advanced Rai stage (projected 5-year OS = 72% and 39% for Rai < or = 2 and Rai > 2; P = 0.01). DAP kinase was methylated in 18 (36%) patients while p14 and Apaf-1 were completely unmethylated in all the primary CLL samples. There was no correlation between DAP kinase hypermethylation and age, sex, poor-risk karyotype, lymphocyte count and Rai stage at diagnosis. Projected OS for patients with and without DAP kinase hypermethylation were 59 and 57% (P = 0.91). DAP kinase, but not p14 and Apaf-1, of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway is frequently hypermethylated in CLL, but not of prognostic significance. Moreover Chinese patients with CLL share a similarly indolent clinical course, and this is the first comprehensive study on p14, DAP kinase and Apaf-1 hypermethylation in CLL.
Adult↗
Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients.
BACKGROUND: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2, respectively. AIM: To study the role of methylation in the inactivation of CKI in chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Methylation-specific polymerase chain reaction was carried out on DNA obtained from the bone marrow of 56 newly diagnosed patients with CLL. RESULTS: Similar demographic features and clinical outcome were observed in our patients when compared with Caucasian patients, including an indolent clinical course (10-year overall survival 51%) and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12 and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%) CLL samples harboured concurrent methylation of both p15 and p16. Apart from an association of p16 methylation with higher presenting leucocyte count (64.5 x 10(9)/l in methylated p16 and 16.0 x 10(9)/l in unmethylated p16 patients; p = 0.016), there was no association between p15 and p16 methylation and age, sex and Rai stage. No difference was observed in the overall survival for patients with and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4 (7.1%) patients, methylation of p21 and p27 was uniformly absent. CONCLUSION: p15 and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP family, were targeted by methylation in CLL. p16 methylation was associated with a higher lymphocyte count at presentation. This is the first comprehensive study of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in Chinese patients with CLL.
Adult↗
Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia.
The Wnt pathway has been shown recently, to be activated in patients with chronic lymphocytic leukemia (CLL). This is the first study to examine the role of Wnt inhibitory factor-1 (Wif-1) methylation in the pathogenesis of haematolymphoid malignancies. Wif-1, a putative tumor suppressor, is a soluble negative regulator of the Wnt pathway activated in CLL. We studied the role of methylation of Wif-1 in 43 Chinese patients with CLL. At diagnosis, Wif-1 methylation was detected in 5/43 (11.6%) CLL marrow samples. Wif-1 methylation occurred more frequently in patients with advanced age (p = 0.059) but there was no correlation between Wif-1 methylation and sex, lymphocyte count and Rai stage at diagnosis. In conclusion, Wif-1 is infrequently methylated in CLL. Other factors leading to activation of the Wnt pathway warrant further study.
Adaptor Proteins, Signal Transducing↗
Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation.
A 52-year-old man developed essential thrombocythemia (ET) with JAK2 V617F mutation after orthotopic liver transplantation (OLT). Retrospective analysis showed that, despite a low platelet count, the JAK2 mutation was already found at presentation 14 months before OLT. The high platelet count that would have been typical of ET might be masked by the cirrhosis-related hypersplenism. Thrombocythemia became obvious after OLT. The patient subsequently developed blastic transformation 12 months afterward, a process probably accelerated by the immunosuppression required for the OLT.
Amino Acid Substitution↗
Long-term donor health and its relationship with outcome of allogeneic hematopoietic stem cell transplantation.
Data on long-term follow-up of donors for hematopoietic stem cell transplantation (HSCT) are limited. Donors of 612 adult allogeneic HSCT were studied, at a median of 81 (14-181) months post-HSC donation. Nine donors had severe health problems. Five donors died from aggressive malignancies or terminal illness, at a median of 41 (16-57) months post-donation. Notably, all their recipients had leukemic relapses. In contrast, donors of recipients in remission were all living. This observation might be due to an inherent depressed immunosurveillance in the donors, or selection of donors with suboptimal health for desperate patients with poor risks pre-HSCT.
Adolescent↗
A prospective study of respiratory ciliary structure and function after stem cell transplantation.
We prospectively investigated the morphological and ciliary function abnormalities in 19 consecutive Chinese patients undergoing hemopoietic stem cell transplantation (HSCT) and studied their relationship with pulmonary complications. The percentage of structural ciliary abnormalities preceding HSCT was comparable to normal controls, but increased up to 1-year post-HSCT. However, the abnormalities did not correlate with ciliary or pulmonary function. Ciliary beat frequency (CBF) for patients undergoing autologous and allogeneic SCT was lower than that of matched controls, with a further decline at one year. There was, however, no significant change in pulmonary function for the whole cohort. There was considerable variation in CBF and ciliary abnormalities in all cases during 3-month interval assessments. Regular ciliary assessment did not predict the only two patients who eventually suffered from bronchiolitis obliterans (BO). We conclude that structural and functional ciliary abnormalities are common in recipients of HSCT, and predict post-HSCT deterioration. However, there is no evidence to show that CBF monitoring may be of prospective benefit.
Adult↗
Aberrant gene promoter methylation marking disease progression in multiple myeloma.
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Antineoplastic Combined Chemotherapy Protocols↗
Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population.
The -308 GA promoter polymorphism of tumor necrosis factor alpha (TNFalpha) has been reported to be associated with an increased risk of lymphoid malignancies in Caucasians. We studied the incidence and prognostic significance of this polymorphism in Chinese patients with plasma cell myeloma (PCM), chronic lymphocytic leukemia (CLL) and lymphomas. Despite a far lower incidence of PCM and CLL in the Chinese population compared with Caucasians, the rates of TNFalpha-308A were similar to those in Caucasians, both in the study and control populations. Similarly, there was no increased rate of TNFalpha-308A in all the lymphomas studied, irrespective of lineage. However, TNFalpha-308A is significantly associated with female CLL cases and confers a strong negative prognostic impact for Chinese CLL. These argue for a possible biological role for increased TNFalpha production in CLL progression in low-risk individuals.
Adult↗
Hyperbilirubinemia and cholelithiasis in Chinese patients with hemoglobin H disease.
Hemoglobin H disease (HbH) is a hemoglobinopathy peculiar to parts of the world with high incidence alpha-thalassemia mutations. Among 90 HbH cases, 50 cases suffered from clinically significant jaundice (bilirubin >30 mmol/l), including 14 with severe jaundice (bilirubin >60 mmol/l). Cholelithiasis was found in 38 cases. The incidence is roughly eight times higher than that in background control population but 50% lower than that in beta-thalassemia. The risk of gallstones was related to higher bilirubin levels but not alpha-globin genotype, sex, ferritin, and hemoglobin levels. Homozygotes or double heterozygotes for Gilbert alleles (17.2%), but not heterozgyotes (42.2%), were found to have a significantly increased risk of gallstones and jaundice. However, common Chinese Gilbert syndrome alleles do not completely explain the variable risks.
Alleles↗
Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy.
BACKGROUND: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. AIMS: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. METHODS: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. RESULTS: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001). CONCLUSIONS: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation.
Adult↗
Molecular epidemiology of follicular lymphoma in Chinese: relationship with bcl-2/IgH translocation and bcl-6 397G/C polymorphism.
The relative incidence of follicular lymphoma (FL) compared with diffuse large B-cell lymphoma (DLCL) is low in Chinese. This may be due to a lower incidence of t(14;18)-mediated disease, a rapid transformation of FL to DLCL, or a lower incidence of FL-prone genetic polymorphisms (e.g., bcl-6 G397C). Using a conventional and long-distance polymerase chain reaction technique, we showed that 93% (43/46) of Chinese FL cases are t(14;18) related and are molecularly indistinguishable from Caucasian cases. The translocation was uncommonly found in Chinese DLCL cases (8/58, 14%). Furthermore, the incidence of bcl-6 hypermutation in FL and DLCL cases appeared to be comparable. These data do not suggest a high incidence of transformation from FL to DLCL in Chinese. Sequencing study also did not show an increased incidence of G397C polymorphism (heterozygote+homozygotes) in FL compared to a population with Chinese background or DLCL cases (25+5% vs 30+4% vs 22+3%). The reasons for the lower incidence of FL in Chinese remain unanswered.
Adult↗
Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation.
Autoimmune thyroid disease (AITD) may occur in patients after hematopoietic stem cell transplantation (HSCT). In all, 10 cases of AITD (seven allogeneic and three autologous HSCT) were diagnosed among 721 HSCT recipients, including two patients with sequential hyper- and hypothyroidism. The 5-year actuarial rates for AITD after allogeneic and autologous HSCT were 2.9 and 4%, respectively. Significant risk factors included HSCT for chronic myeloid leukemia, the HLA B46 and DR9 loci and the A2B46DR9 haplotype, while female donors showed trend to significance. On multivariate analysis, only female donors and HLA DR9 remained significant. For autologous HSCT, the associations with HLA B46 and DR9 were also significant. Only three donors had a family history of AITD. A review of other reported cases confirmed the predominance of female donors, although the other associations including graft-versus-host disease, familial AITD and other autoimmune phenomena might be related to reporting bias. Since the actuarial incidence of AITD from female donors with predisposing HLA alleles may be over 30%, susceptible recipients should be carefully monitored. Owing to the small number of reported cases and different HLA associations with AITD in different populations, our observations await confirmatory data from other registries.
Adult↗
siRNA targeting the leader sequence of SARS-CoV inhibits virus replication.
SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.
5' Untranslated Regions↗
Thrombocytopenia after gemtuzumab is reversible by intravenous immunoglobulin.
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Aged↗
Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma.
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Adult↗
Primary anaplastic large cell lymphoma of the pancreas.
Most solid pancreatic tumors are exocrine adenocarcinomas. We presented a patient with primary ALCL of the pancreas masquerading as a carcinoma of the head of pancreas. She was scheduled for a Whipple's operation and the intra-operative frozen section showed anaplastic carcinoma. The proper diagnosis was only derived later with CD30 immunohistochemical study. This carries important implications on the management, as radical surgery is indicated in resectable carcinoma but not for a chemosensitive lymphoma.
Adult↗
Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years.
BACKGROUND: Data on mature T-cell and natural killer (NK)-cell lymphomas diagnosed with the World Health Organization (WHO) classification scheme are scarce. They are regarded to be more common in Asian populations. METHODS: Consecutive T-cell and NK-cell lymphomas classified according to the WHO scheme within 10 years in a Chinese population were reviewed. RESULTS: There were 148 cases, constituting 16.6% (T-cell, n=90, 10.1%, NK-cell, n=58, 6.5%) of all non-Hodgkin lymphomas in this period. There was a male predominance (male:female = 2.5), young age at diagnosis (median age 50 years, range 8-86) and frequent extranodal presentation. Commonest T-cell lymphomas included anaplastic large cell lymphoma (ALCL, n=25, median age 35 years, nodal 60%, stage I/II 60%), peripheral T-cell lymphoma, unspecified (PTCL, n=24, median age 54 years, nodal 42%, stage I/II 42%), and angioimmunoblastic T-cell lymphoma (AILT, n=19, median age 67 years, nodal 95%, stage I/II 26%). Overall frequencies of T-cell lymphomas were comparable to Western patients. AILT, PTCL and ALCL were aggressive with a poor outcome. NK-cell lymphomas were predominantly extranodal (96%) and aggressive, with a frequency much higher than Western patients. CONCLUSIONS: The apparent high prevalence of T-cell and NK-cell lymphomas in the Chinese was due to more frequent NK-cell but not T-cell lymphomas.
Adolescent↗