OBJECTIVE: To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL). METHODS: The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed. RESULTS: 144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL. CONCLUSION Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.
Adult ; Humans ; Lymphoma, Mantle-Cell/genetics* ; Bone Marrow/pathology* ; Leukemia/pathology* ; Mutation ; Immunophenotyping

Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.
Aged ; Cyclin D1/genetics* ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphoma, Mantle-Cell/pathology* ; Male ; Middle Aged ; Molecular Biology

OBJECTIVE: To investigate the expression of Circ_cgga162 in serum of mantle cell lymphoma (MCL) patients and analyze its potential as a prognostic biomarker. METHODS: The expression of Circ_cgga162 in 86 cases of mantle cell lymphoma and 50 cases of lymph node reactive hyperplasia (RH) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). The relationship between the expression of Circ_cgga162 and clinicopathological features was analyzed by univariate analysis. The relationship of Circ_cgga162 expression with progression-free survival time and overall survival time was analyzed by Kaplan-Meier. The relationship between expression of Circ_cgga162 and prognosis of patients was analyzed by univariate and multivariate analysis. RESULTS: The expression level of Circ_cgga162 in MCL patients was significantly higher than that in control (RH) group (P＜0.01). The expression of Circ_cgga162 not correlated with age, gender, B symptoms and LDH (all P＞0.05), but correlated with the expression of MCL International Prognostic Index (IPI), Ann Arbor stage, bone marrow infiltration and Ki67 (all P＜0.05). In addition, Kaplan-Meier analysis showed that the progression-free survival time and overall survival time of the MCL patients with high expression of Circ_cgga162 were significantly shorter than those of the MCL patients with low expression (P＜0.01). Univariate analysis showed that Ann Arbor stage, Circ_cgga162 expression, MIPI, bone marrow infiltration and Ki67 were the prognostic factors for MCL patients (all P＜0.05). Multivariate Cox regression analysis showed that Ann Arbor stage, Circ_cgga162 expression and MIPI were independent factors affecting the prognosis of MCL patients (all P＜0.05). CONCLUSION Circ_cgga162 is highly expressed in serum of patients MCL, which relates with the prognosis of MCL patients. Circ_cgga162 can be used as a potential prognostic marker and therapeutic target for MCL patients.
Humans ; Kaplan-Meier Estimate ; Lymphoma, Mantle-Cell ; Multivariate Analysis ; Prognosis ; RNA, Circular ; genetics

OBJECTIVE: To explore the expression level of PLK1 in mantle cell lymphoma(MCL), and the effect of silencing PLK1 gene by RNA interference on the cell proliferation, apoptosis, and cell cycle. METHODS: S-P immunohistochemistry technique was used to detect the expression of PLK1 in tissues of 42 patients with MCL and 30 patients with reactive proliferative lymphodenitis(RPL), their expression levels were compared and analyzed. The Jeko-1 cells were transfected with lentivirus contaiming PLK-1 shRNA, then the mRNA and protein expression of PLK-1 was detected by real-time guantitative PCR and Western blot nespectively, and the silencing efficacy of PLK-1 shRNA was identificd. The cell proliferation was detected by CCK method, the cell apoptosis was detected by Annexin V/PI double staining, the cell cycle was detected by PI single staining, the changes of apoptosis-related proteins BAX, BCL-2 and Caspase 3 were detected by Western blot. RESULTS: The positive expression rate of PLK-1 in tissue of MCL patients was 66.67%(28/42), which was significanfly higher than 20%(6/30) in tissue of RPL patients (P＜0.05). The PLK-1 positive expression correlated with B symptom, IPI score, Ann-Arbor stage(P＜0.05). After infection of Jeko-1 cells with lentivirus containing PLK-1 shRNA for 72 hours, the mRNA and protein expressions of PLK-1 were significantly down-regulated(P＜0.05), the proliferation rate of cells in group of PLK-1 shRNA was significanly lower than that in control and Neg shRNA groups(P＜0.05); the apoptosis rate of cells in PLK-1 shRNA group was (27.42±3.44)%, which was significantly higher than that in control group (1.23±0.42)% and Neg shRNA group (2.07±0.58) % (P＜0.05). The cell cycle analysis showed that the cell ratio in G/M phase of PLK-1 shRNA group was (27.21±3.59) %, which was higher than that in control group (13.28±2.63)% and Neg shRNA group (14.34±2.37) %. The detection of apoptosis-related proteins showed that the expression of BAX was up-regulated, the expression of BCL-2 was down-regnlated and the expression of caspase 3 was up-regulated. CONCLUSION The PLK-l overexpression appears in tissue of MCL patients. The silencing PLK-1 gene can inhibit the proliferation of Jeko-1 cells, induce the apopotosis of Jeko-1 cells and arrestes cell cycle in G/M phase.
Apoptosis ; Cell Cycle Proteins ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma, Mantle-Cell ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Proto-Oncogene Proteins ; genetics ; RNA, Small Interfering

OBJECTIVE: To investigate the expression of miR-101 and EZH2 in patients with mantle cell lymphoma(MCL) and to analyze its correlation with clinical prognosis of MCL patients. METHODS: RQ-PCR and S-P immunohistochemistry were used to detect the expressions of miR-101 and EZH2 in tissue of MCL patients. CCK-8 was used to assay the effect of miR-100 minics on the proliferation of Jeko-1 and Mino cells; the flow cytometry with Annexin V/PI double staining was used to assay the apoptosis; Western blot was used to assay the effect of miR-101 minics on the expression of EZH2 protein in Jeko-1 and Mino cells. RESULTS: Compared with control group, miR-101 lowly expressed, and EZH2 protein highly expressed in MCL group, with very statistically significant difference(P<0.01).There was negative correlation between miR-101 and EZH2 expression(r=-0.638，P<0.05). The expression of miR-101 and EZH2 significantly correlated with B symptoms, International Prognostic Index(IPI) and Ann Arbor stage, respectively. Survival analysis showed that the overall survival(OS) rate of patients with low expression of miR-101 were significantly lower than that of patients with high miR-101 expression (P=0.0014), the OS rate of patients with EZH2 high expression were significantly lower than that of patients with EZH2 low expression (P=0.0093). The miR-100 minics could inhibit the proliferation of Jeko-1 and Mino cells, and increase the apoptotic rate. The expression of EZH2 protein was markedly suppressed by the miR-100 minics. CONCLUSION The expression of miR-101 and EZH2 is different in MCL patients with different clinical stage and prognosis. The miR-101 can inhibit the cell proliferation and induce cell apoptosis of mantle cell lymphoma by targeting EZH2.
Apoptosis ; Cell Proliferation ; Enhancer of Zeste Homolog 2 Protein ; genetics ; Humans ; Lymphoma, Mantle-Cell ; genetics ; MicroRNAs ; genetics ; Prognosis

OBJECTIVETo study the clinical features and diagnosis of 7 patients with atypical mantle cell lymphoma (MCL).

METHODSThe 7 MCL patients were misdiagnosed as chronic lymphocytic leukemia (CLL) due to a score of 4 for their immunophenotypes. The clinical features and diagnosis of such patients were retrospectively analyzed.

RESULTSSix patients had superficial lymphadenectasis but their lymph nodes could not be palpated. All 7 patients were as stage IV considering bone marrow infiltration. Scores of immunophenotype of CLL were 4, and interphase fluorescence in situ hybridization (FISH) for t(11;14) were positive in all patients.

CONCLUSIONSome MCL patients have clinical features similar to CLL. Interphase FISH can play an important role in the diagnosis of MCL.

Aged ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoma, Mantle-Cell ; diagnosis ; genetics ; Male ; Middle Aged ; Translocation, Genetic

OBJECTIVETo study the relationship between immunoglobulin variable heavy chain (IgVH) gene mutation status and clinical features, pathologic findings and biologic behavior of mantle cell lymphoma (MCL).

METHODSIgVH gene was amplified in 60 cases of MCL with FR1-JH and FR2-JH primers in BIOMED-2. The sequence was determined by cloning. The IgVH somatic mutational status was analyzed using NCBI's Ig-Blast tool. The relationship between IgVH gene mutation status and clinicopathologic features was also analyzed.

RESULTSForty percent (24 cases, 28 functional Ig genes) of the MCL cases displayed somatically mutated VH genes (defined as > 2% mutated), whereas 60.0% (36 cases, 40 functional Ig genes) showed unmutated VH genes. The most widely used genes were VH3-21 (27.9%) and VH4-34 (19.1%). The former were mainly used by unmutated cases, while the later mainly by mutated cases.Intraclonal heterogeneity was noted in 19 cases. There was no correlation of VH mutation status and specific VH gene with survival (P > 0.05).

CONCLUSIONSMCL comprises at least two subsets that do not correlate with morphology: one with unmutated VH genes and one with mutated VH genes. The biased use of VH3-21 and VH4-34 is noted. The nonrandom usage of IgVH segments suggests specific antigens may play a role in the pathogenesis and progression of MCL subsets. There is no correlation of IgVH mutation status and specific VH gene with survival.

DNA Primers ; Female ; Genes, Immunoglobulin Heavy Chain ; genetics ; Humans ; Immunoglobulin Variable Region ; genetics ; Lymphoma, Mantle-Cell ; genetics ; mortality ; pathology ; Male ; Mutation ; Prognosis

The study was purposed to investigate the effect of silencing NOTCH1 gene by shRNA interference on the proliferation, apoptosis and the expression of AKT signaling pathway-related proteins in mantle cell lymphoma Jeko-1 cell line. The hairpin-like oligonucleotide sequences targeting NOTCH1 gene were designed and transfected into Jeko-1 cells by lipofectamine (TM) 2 000. NOTCH1 mRNA and protein were detected respectively by RT-PCR and Western blot. Cell growth was determined by MTT. Cell apoptosis was analyzed by flow cytometry. The expressions of BCL-2, BAX, procaspase-3, procaspase-9, Akt, p-Akt, p-mTOR, p-P70S6K were detected by Western blot. The results showed that NOTCH1 mRNA expression was markedly suppressed by the shRNA targeting NOTCH1. NOTCH1 shRNA suppressed the proliferation of Jeko-1 cells and induced apoptosis of these cells. The cell apoptotic rate was (34.5 ± 3.4)%, (2.4 ± 1.3) %, (1.7 ± 0.6) % in NOTCH1 shRNA, Neg-shRNA and blank groups, respectively, and the difference between them was statistically significant (P < 0.01). NOTCH1 shRNA down-regulated the expression of BCL-2, procaspase-3, procaspase 9, p-Akt, p-mTOR and p-70S6K, up-regulated the expression of BAX, but no change protein expression of Akt was observed. It is concluded that the silencing NOTCH1 gene expression by shRNA interference may inhibit Jeko-1 proliferation, induce the cell apoptosis, and the mechanisms may be associated with the inhibition of Akt/mTOR signaling pathway by dephosphorylation.
Apoptosis ; Caspase 3 ; Caspase 9 ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma, Mantle-Cell ; genetics ; Proto-Oncogene Proteins c-akt ; RNA, Messenger ; RNA, Small Interfering ; genetics ; Receptor, Notch1 ; genetics ; Signal Transduction ; TOR Serine-Threonine Kinases ; Transfection

Humans ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Signal Transduction

Humans ; Lymphoma ; classification ; genetics ; pathology ; Lymphoma, Follicular ; genetics ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; pathology ; Lymphoma, Mantle-Cell ; genetics ; pathology ; World Health Organization