Non-Hodgkin's lymphoma (NHL) is a malignant tumor originated in lymphatic hematopoietic tissue. At present, chemotherapy is the main treatment method of NHL, but the chemoresistance is still an important reason for NHL treatment failure. The mechanism of NHL multidrug resistance (MDR) is complex, involving a variety of singnal pathways, in which mutation in the genetic level of the key genes can result in tumor cell resistance phenomenon. MicroRNA are small non-coding RNA that can be widely detected in plants,animal species and viruses. They regulate protein expression by repressing translation mRNA target at the post-transcriptional level, participating in the differentiation and development of tumor cells, as well as the occurrence and development of tumor, the change of the expression level microRNA plays an important role in the genesis and chemoresistance mechanism of NHL. Therefore, the intervening factitiously the expression level of microRNA in NHL through manufacturing antisense oligonucleotide (AMO) or using substitution of microRNA, changing the expression level of their target protein, and combining with the therapy of NHL, there will be an guiding significance in reversing the drug and radiation resistance of NHL, thus improving its poor prognosis. This article reviews the microRNAs closely related with drug and radiation resistance of NHL, and their potential targets. Furthermore, the specific role of these microRNAs in the genesis and chemoresistance mechanism of NHL are deeply elaborated.
Animals ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Lymphoma, Non-Hodgkin ; drug therapy ; genetics ; MicroRNAs ; genetics

OBJECTIVETo explore the clinical values of detecting immunophenotype and analyzing DNA ploid by flow cytometry for patients with non-Hogkin's lymphoma (NHL).

METHODSEighty NHL patients admitted in our hospital from August 2007 years to March 2015 Years were included in the observation group, 20 patients with reactive lymphoid hyperplasias were selectod as control group. The immunophenotypes were detected and the DNA ploid was analyzed by flow cytometry.

RESULTSThe detected rate of DNA aneuploidy, DAN index (DI) and SPF in observation group were higher than those in control group, there was signifificant difference (P < 0.05). The SPF and DI in patients with NHL-I, NHL-II had no statistical difference as compared with that in control group (P > 0.05); but the SPF and DI in pateints with NHL-III and patients with NHL-IV showed statistical significance as compared with that in control group (P < 0.05). The SPF and DI in patients with low malignancy group and middle malignancy group showed statistical significance as compared with control group (P < 0.05). The SPF and DI in middle malignancy group had statistical significance as compared with that in low malignancy group (P < 0.05).

CONCLUSIONthe immunophenotype detection and DNA ploid analysis by flow cytometry can reflect the tumor proliferation and deterioration of patients with Non-Hogkin's lymphoma, predicting the prognosis.

Aneuploidy ; Case-Control Studies ; DNA ; Flow Cytometry ; Humans ; Immunophenotyping ; Lymphoma, Non-Hodgkin ; classification ; genetics ; Ploidies ; Prognosis

Non-Hodgkin's lymphoma (NHL) is a heterogenous disease from various resources and biological characters. Many researches indicated molecular abnormal characteristics in patients with NHL. Currently, NHLs are diagnosed according to the World Health Organisation classification. With the advances in molecular biology and cytogenetics, the cell as a morphological and functional unit has become essential in the diagnosis, therapy and prognosis of lymphoma. The signification of abnormal karyotypes has been more and more focused on, and great progression has been made. Accepting the pitfalls of conventional cytomorphology and immunophenotype, this review emphasizes molecular abnormalities in non -Hodgkin's lymphomas, which are not only a molecular characterization, but also an indicator to predict prognosis and response to treatment.
Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Humans ; Lymphoma, Non-Hodgkin ; genetics

OBJECTIVETo investigate the role of cytogenetic analysis in the detection of bone marrow (BM) involvement in patients with non-Hodgkin's lymphoma (NHL).

METHODSThe bone marrow samples of 74 patients with NHL were detection by using morphology, cytogenetic test, flow cytometry and molecular biological assay. The detected results of morphology, cytogenetic test, flow cytometry and molecular biological assay alone and thier combined detection were compared, the detective rate and consistencies of the 4 methods were analyzed.

RESULTSThe detection rates of BM involvement by using morphology, cytogenetic, flow cytometry, and molecular biological assays were 21.6%, 17.6%, 23.0% and 33.8% respectively. The detective rate was enhanced to 44.6% by combining the 4 methods. Cytogenetic test showed the result consistent with the other methods.

CONCLUSIONAlthough cytogenetic test shows a lower detective rate than the other methods, but in some patients the cytogenetic test can detect the abnormality of bone marrow which can not be detected by other methods alone, the combination test of 4 detection methods can enhance the detectable rate of BM involvement.

Bone Marrow ; pathology ; Bone Marrow Examination ; Cytogenetic Analysis ; Flow Cytometry ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; genetics

To determine whether the p53 expression might be a predictor for treatment sponse and overall survival in nodal non-Hodgkin's lymphoma (NHL), we analyzed e expression of p53 in 69 NHL patients. p53 protein expression was analyzed by munohistochemistry with long-term follow up (1-148 months: median 12.2). p53 pression was noted in 23/69 (33.3%) patients. Complete response (CR) rate to stemic chemotherapy was correlated with stage (I/II) (p=0.038), but not with 3 expression (p=0.2856). Poor overall survival was associated with stage =0.0010) or IPI score (p=0.0076), but not with p53 expression (p=0.8601). From ratification analysis by stage, in stage III/IV patients, the p53 positive oup had a trend to be associated with poor overall survival than the p53 gative group. Multivariate analysis revealed that p53 positive group was sociated with less CR rate compared to the p53 negative group (p=0.046), ereas overall survival was correlated with stage (p=0.0320), not with p53 atus. p53 expression was associated with less CR rate in patients with DLBL. rther studies with large numbers of samples and homogenous group of NHL are eded to determine the prognostic value of cell cycle regulator, p53 in NHL.
Antibodies, Monoclonal ; Cell Cycle Proteins/biosynthesis ; Female ; Gene Expression ; Human ; Immunohistochemistry ; Immunophenotyping ; Lymph Nodes/pathology* ; Lymph Nodes/metabolism* ; Lymphoma, Non-Hodgkin/pathology* ; Lymphoma, Non-Hodgkin/metabolism* ; Lymphoma, Non-Hodgkin/genetics ; Lymphoma, Non-Hodgkin/drug therapy ; Male ; Middle Age/Mpartment of Microbiology ; Prognosis ; Protein p53/immunology ; Protein p53/genetics ; Protein p53/biosynthesis*

The aim of this study was to evaluate the significance of id4 gene promotor methylation detection in NHL patients. MS-PCR method was used to detect the status of id4 gene methylation in health donors and newly diagnosed NHL patients. The results indicated that the id4 gene was unmethylated in bone marrow samples from health donors. Among 18 newly diagnosed NHL patients, including one NHL patient with bone marrow cells involved, 4 patients were found in id4 gene methylation by MS-PCR. The 14 patients with id4 gene unmethylation were in their stable status and no bone marrow involvement were found by bone marrow biopsy during the 8-month follow-up. During the follow-up, the patient with both bone marrow involvement and id4 gene methylation turned to leukemia, in 2 out of the 3 patients with id4 gene methylation but without bone marrow involvement at diagnosis, the bone marrow involvement was found at last. It is concluded that the id4 gene methylation may be an indicator for MRD in NHL patients without bone marrow involvement.
Bone Marrow ; pathology ; DNA Methylation ; Humans ; Inhibitor of Differentiation Proteins ; genetics ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Promoter Regions, Genetic ; genetics

Paraffin-embedded tissue samples from 30 cases of non-Hodgkin's lymphoma(NHL) and 10 of reactive hyperplasia, were processed for interphase cytogenetic chromosomal study. We performed non-fluorescent in situ hybridization(NFISH) using the enzymatic method with digoxigenin-labeled DNA centromeric probes for chromosome 7,12,18 and X, and a painting probe for chromosome 18. Chromosomal aberrations were observed in 27(90%) out of 30 cases of NHL. The most commonly observed numerical aberration was extracopy of X chromosome. There were some characteristic aberrations corresponding to each grade and group of NHL by International Working Formulation: In low grade NHL(9 cases), a third were associated with extracopy of chromosome 12, and disomy X was frequently found in small lymphocytic lymphoma(75%). With intermediate grade(16 cases), tetraploidy(25%), translocation of chromosome 18(25%), and extracopy of chromosome 18(19%) were characteristically associated. These results suggest that interphase NFISH is an easily performable method in retrograde cytogenetic study of archival materials. Some specifically correlated chromosomal aberrations corresponding to the histopathologic grades and groups could provide us more valuable information for determining pathologic diagnosis and assessing the clinical outcome of NHL.
*Chromosome Aberrations ; Human ; Immunophenotyping ; *In Situ Hybridization ; Interphase ; Lymphoma, Non-Hodgkin/*genetics/pathology ; Paraffin Embedding ; Pseudolymphoma/genetics/pathology

OBJECTIVE: To investigate the relationships between caspase-8 (CASP8), fatty acid synthetase (Fas) gene polymorphisms and prognosis of non-Hodgkin's lymphoma patients in Han nationality. METHODS: The clinical data of 85 patients with non-Hodgkin's lymphoma were analyzed retrospectively. The polymorphisms of CASP8 and Fas gene were detected, and prognosis of the patients were analyzed. The polymorphisms of CASP8 and Fas gene in patients with different prognosis were compared, and the relationships between gene polymorphisms and the poor prognosis of the patients were investigated. RESULTS: The incidence rate of poor prognosis of the patients enrolled in the study was 65.88%. The polymorphisms of CASP8 and Fas genes in the patients with poor or good prognosis were in accordance with Hardy Weinberg's law of genetic balance. The frequencies of GG genotype and G allele at rs 1035142 of CASP8 gene, GA genotype and A allele at rs 1377 of Fas gene in patients with poor prognosis were lower than those of the patients with good prognosis (P<0.05). The frequencies of GT, TT and T alleles at rs 1035142 of CASP8 gene, GG and G alleles at rs 1377 of Fas gene in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). The proportions of Ann Arbor stage III-IV and high malignancy in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). Logistic multiple regression analysis showed that Ann Arbor stage III-IV, moderate malignant, high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype were all the risk factors for the poor prognosis of the patients (P<0.05). CONCLUSION The poor prognosis rate of non-Hodgkin's lymphoma patients in Han nationality is relatively high, and the risk factors for the prognosis of the patients include Ann Arbor stage III-IV, moderate and high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype.
Caspase 8/genetics* ; Ethnicity ; Fatty Acids ; Humans ; Ligases ; Lymphoma, Non-Hodgkin/genetics* ; Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; fas Receptor

The study was aimed to investigate the BCL-XL expression and mutation, and its clinical significance in non-Hodgkin's lymphoma. Lymphoma cells were selectively isolated by laser microdissection. BCL-XL expression from lymphoma tissue and microdissected lymphoma cells was measured by using real-time quantitative reverse transcription-polymerase chain reaction. BCL-XL mutation was analyzed by using direct sequencing of PCR products. The results showed that compared to 15 patients with reactive hyperplasia, BCL-XL was overexpressed in follicular lymphoma (n = 30), both in lymphoma tissue (P = 0.0064) and in microdissected lymphoma cells (P < 0.0001). No significant rise of BCL-XL expression was observed in patients with T-cell lymphoma (n = 24) and diffuse large B cell lymphoma (n = 24). In follicular lymphoma, high BCL-XL level was associated with multiple extranodal involvement (P = 0.0004), elevated lactate dehydrogenase level (P = 0.0019), high-risk international prognostic index (P = 0.0013) and a short overall survival time (P = 0.0451). Mutation analysis revealed one synonymous mutation (Codon 109 ACA-->ACC) in one case of follicular lymphoma patient. It is concluded that BCL-XL expression is closely correlated with progress of follicular lymphoma and prognosis of patients with follicular lymphoma. The value of BCL-XL expression as a prognostic marker in follicular lymphoma should be considered.
Base Sequence ; Humans ; Lymphoma, Follicular ; genetics ; pathology ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Molecular Sequence Data ; Point Mutation ; bcl-X Protein ; biosynthesis ; genetics

Epstein-Barr virus(EBV) has been implicated in the pathogenesis of B-lymphoproliferative disorders, T-cell lymphomas and Hodgkin's disease. In this report, we performed an in situ hybridization study on EBV genome in 10 cases of nasal non-Hodgkin's lymphoma(NHL), 20 cases of Waldeyer's ring(WR) NHL, and 20 cases of nodal NHLs to document EBV association with lymphomas in Koreans. For immunophenotyping, monoclonal antibodies for CD 20, MB 2, CD 45Ro & CD 43 were used. For in situ hybridization study, EBV DNA probe for Bam HI 'V' fragment and EBV RNA probe for EBER and BHLF were used. Twenty two cases(44%) of malignant lymphomas were positive for EBV genome. Generally, T-cell lymphomas showed a higher positive rate(61%) than B-cell lymphomas(24%). Among T-cell lymphomas, nasal lymphomas showed a higher positive rate(80%) than WR(50%) or nodal lymphomas(50%). Of 22 EBV genome positive cases, 10 cases were positive for EBER, 10 cases for BHLF, and 2 cases for both EBER and BHLF. The histologic types by Working Formulation(WF) were not correlated with EBV genome positive rate, whereas lymphomas showing the histologic spectrum of polymorphic reticulosis(PR) showed a higher positive rate(65%) than lymphomas without PR-like features(40%). These results indicate that nasal T-cell lymphomas with the histologic spectrum of PR are strongly associated with EBV and that the anatomic site may be an important factor in this association.
DNA, Viral/analysis ; Genome, Viral ; Herpesvirus 4, Human/*genetics ; Human ; *In Situ Hybridization ; Lymphoma, Non-Hodgkin/*virology ; RNA, Viral/analysis