Mantle cell lymphoma (MCL) is a rare B-cell lymphoma characterized by both the incurable nature of indolent lymphomas and the clinical course of aggressive lymphomas. The integration of high-dose cytosine arabinoside (Ara-C) and autologous hematopoietic stem cell transplantation (ASCT) has led to substantial improvement in the outcomes of MCL patients in the immunochemotherapy era. More recently, the widespread use of small molecule targeted agents, particularly Bruton tyrosine kinase inhibitor (BTKi), has re-shaped the therapeutic landscape of MCL patients and challenged the traditional role of high-dose Ara-C and ASCT. Novel immunotherapies including bi-specific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy have emerged as important treatment options for MCL patients with relapsed or refractory disease. With advances in multi-omics profiling, the development of personalized, potentially curative strategies based on individual genetic and immune features is expected to become a major focus of future research on MCL. This article will delve into the latest research progress in the treatment and genetics and translational research on MCL patients, focusing on the latest progress of research on the treatment of newly diagnosed MCL patients, treatment of relapsed/refractory MCL patients, and the genetics and translational treatment of MCL patients, and explore the evolution and future direction of its treatment model.
Humans ; Lymphoma, Mantle-Cell/immunology* ; Translational Research, Biomedical ; Hematopoietic Stem Cell Transplantation ; Immunotherapy

OBJECTIVETo explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.

METHODSImmunophenotyping of bone marrow and (or) of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodies, and the patients clinical data were retrospectively analyzed. The difference in immunophenotypes and the related clinical features were retrospectively analyzed. Fluorescence in situ hybridization (FISH) for t(11;14) detection was applied to diagnose or exclude mantle cell lymphoma.

RESULTS(1)A total 260 CD5⁺ B-LPD patients were enrolled in this study, including 186 chronic lymphocytic leukemia (CLL), 40 mantle cell lymphoma (MCL), other B-LPD including 5 splenic marginal zone lymphoma (SMZL), 2 B-cell prolymphocytic leukemia (B-PLL), 3 hairy cell leukemia (HCL). The other 26 cases (10%)were not classified and defined as unclassified B-LPD (BLPD-U). MCL patients were all positive for t(11;14) detected by FISH, while all the BLPD-U patients were negative for t(11;14). (2) All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, 186 CLL patients scored 4-5, 99.5% of patients with CD23⁺, 11.3% with sIgM⁺, 10.2% with FMC7⁺, 44.1% with CD22⁺ and 51.1% with CD11c⁺. MCL patients scored 2-3, with 50% expressing CD23 and sIgM, 81.6% expressing FMC7, 92.1% expressing CD22 and 5.3% expressing CD11c. In aspect of BLPD-U and other B-LPD, the expression of CD23, sIgM, FMC7, CD22 and CD11c were 73.1% and 50%, 34.6% and 50%, 88.5% and 100%, 92.3% and 90%, 69.2% and 70%, respectively. (3)In comparison of CLL with MCL, there was a significant difference in the expression of CD23, sIgM, FMC7, CD22 and CD11c between the two groups (P<0.01). Between MCL and BLPD-U, similar expression type of CD23, sIgM, FMC7 and CD22 was found except CD11c, which was highly expressed in BLPD-U (P<0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P<0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P<0.01). The expression of CD23 and sIgM in MCL are 7%-21% and 82%-100% respectively in Western population, while the expression of other immunophenotypic markers is similar with our study.

CONCLUSIONThe significant high incidence of CD23 and low incidence of sIgM compared to the Western population was observed in Chinese patients, and CD11c coud serve as a useful marker to distinguish MCL from CLL and other CD5⁺ B-LPD.

Adult ; Aged ; Aged, 80 and over ; Cell Count ; Female ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; immunology ; Lymphoma, Mantle-Cell ; immunology ; Lymphoproliferative Disorders ; immunology ; Male ; Middle Aged ; Retrospective Studies

Mantle cell lymphoma (MCL) is a kind of mature B-cell neoplasms with significantly poor prognosis and is usually misdiagnosed. With the development of flow cytometry and cytogenetic technique, most patients were at leukemic phase when diagnosed. This study was purposed to investigate the immunophenotypes of MCL, the immunophenotype information of 22 leukemic MCL patients was analyzed retrospectively. All the patients were conformed t(11;14) translocation by fluorescence in situ hybridization. Immunophenotypes were detected by a four-color flow cytometry including CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD22, CD23, CD25, CD38, CD103, CD148, CD200, FMC7, ZAP-70, κ, λ. The results showed that CD19, CD5, CD20 and monoclonal sIg expressed in all 22 patients with CD20 high expression; CD22 expressed weakly in 17 patients; CD23 expressed in 6 patients including 2 cases highly expressed; FMC7 expressed in 12 patients. 5 patients were 4-point score and 17 patients had a score less than 4 according to CLL scoring system. CD148 and CD200 were detected in 18 patients, in which CD200 expressed negatively in 11 patients, CD200 expressed weakly in 7 patients with median fluorescence intensity (MFI) 25.8 (6.6 - 254.26); CD148 expressed positively in all 18 patients with median MFI: 337 (73.4 - 1341.9). It is concluded that the atypical immunophenotype is common in leukemia MCL, thereby the diagnosis of MCL needs comprehensively analyze with morphocytology, immunophenotype and cytogenetic, CD200 and CD148 as new bio-markers can differentiate MCL from chronic B cell lymphoproliferative disease.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Female ; Humans ; Immunophenotyping ; Karyotyping ; Lymphoma, Mantle-Cell ; genetics ; immunology ; metabolism ; Male ; Middle Aged ; Receptor-Like Protein Tyrosine Phosphatases, Class 3 ; metabolism ; Retrospective Studies

The coexistence of CCND1/IGH and MYC rearrangements in mantle cell lymphoma (MCL) is a rare finding associated with a very poor prognosis. In this study, a patient with blastoid variant (MCL) is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient only survived for 1 month following diagnosis. Conventional cytogenetic study, FISH, and multicolor FISH (mFISH) demonstrated the involvement of the BCL1/CCND1 locus in a complex translocation, t(3;11)(q25;p15)t(11;14)(q13;q32). In addition, subclonal abnormalities in the 8q24 region, manifested as a t(8;14)(q24;q32)/MYC rearrangement, were identified. To the best of our knowledge, this is the first MCL case in Korea bearing these complex genomic aberrations.
Aged, 80 and over ; Antigens, CD5/*metabolism ; Bone Marrow/immunology/metabolism ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 3 ; Gene Rearrangement ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Lymphoma, Mantle-Cell/*diagnosis/genetics/immunology ; Male ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; Translocation, Genetic

OBJECTIVETo investigate the clinicopathologic features of lymphoplasmacytic lymphoma (LPL) with Waldenström's macroglobulinemia (WM) and to evaluate the usefulness of immunophenotype analysis in diagnosis and differential diagnosis of the tumor.

METHODSA total of 40 cases of LPL with WM diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were analyzed using immunophenotype and follow-up information.

RESULTSThe mostly common initial clinical presentations were non-specific symptoms, such as fatigue, anemia and hemorrhage. Lymphadenopathy, splenomegaly and hepatomegaly were found in 42.5%, 20.0% and 12.5% of the patients respectively. The pattern of bone marrow involvement included mixed type (47.2%), diffuse type (41.7%) and interstitial type (11.1%). The nodal architecture was completely destroyed in one case and partially effaced with residual germinal centers and dilated sinuses in 8 cases. All of the neoplastic cells expressed CD20 and CD79a. Neoplastic plasma cells were positive for CD138 and CD79a. No cases expressed CD5. Four cases weakly expressed CD23. No significant prognosis related factors were identified in the survival analysis.

CONCLUSIONSLPL with WM is a rare indolent small B-cell lymphoma, which is commonly seen, in older male patients. The tumor frequently involves bone marrow and shows various clinical manifestations. Combination analyses of the bone marrow biopsy histology, immunophenotypic study and clinical data, especially the serum examination are important for the diagnosis of LPL with WM.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Bone Marrow ; metabolism ; pathology ; CD79 Antigens ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin M ; blood ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphatic Metastasis ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Invasiveness ; Survival Rate ; Syndecan-1 ; metabolism ; Waldenstrom Macroglobulinemia ; immunology ; metabolism ; pathology

This study was aimed to explore the characteristics of miR-17-92 cluster at chromosome 13q31-q32 in B cell malignant lymphoma and to investigate the changes of miR-17-92 cluster in B cell lymphoma at genome DNA level and its influence on expression of miR-17-92 cluster and relation with lymphoma occurrence. PCR and DNA sequencing were used to detect miR-17-92 cluster at chromosome 13q31-q32 in mantel cell lymphoma (MCL) cell lines Rec1, G519 and Z138. The results showed that DNA sequence of miR-17-92 cluster at chromosome 13q31-q32 in MCL cell lines were normal. It is concluded that there is no abnormal change in DNA sequence of miR-17-92 cluster which is not the mechanism for miR-17-92 cluster overexpression in mantel cell lymphoma cell lines.
Base Sequence ; Cell Line, Tumor ; Chromosomes, Human, Pair 13 ; genetics ; Humans ; Lymphoma, Mantle-Cell ; genetics ; immunology ; MicroRNAs ; genetics ; Molecular Sequence Data ; Sequence Analysis, DNA

OBJECTIVETo investigate the application of flow cytometry in the differential diagnosis of lymphoma/leukemia with aberrant antigen expression.

METHODSThe results of flow cytometry of 30 lymphoma/leukemia cases with aberrant antigen expression, of which 3 cases being lymphomas, 8 B-cell leukemia, 1 T-cell leukemia, 17 acute non-lymphoid leukemia and 1 acute non-lymphoid leukemia involving lymph nodes were analyzed. Immunohistochemistry (EnVision) for CD79a, CD3 and MPO was performed on all cases.

RESULTSEleven cases of B-cell lymphoma/leukemia were cytoplasmic CD79a (cCD79a)-positive, cytoplasmic CD3 (cCD3epsilon) and cytoplasmic MPO (cMPO)-negative. Five of these cases were positive for CD5 and 2 for CD5, 1 or 2 for myeloid marker(s). The T-cell leukemia cases were cCD3epsilon-positive, cCD79a and cMPO-negative, they also co-expressed CD13 and CD33. The mantle cell lymphoma cases were positive for CD3, CD13 and CD33. Of the 8 B-cell leukemia cases, 4 were positive for CD5, 3 for CD13 and 1 for CD13 and CD33. The 18 acute non-lymphoid leukemia cases (including 1 acute non-lymphoid leukemia case involving lymph nodes) were cMPO-positive and cCD79a and cCD3epsilon-negative. Eight of the 18 expressed T-cell markers (including 1 case of acute non-lymphoid leukemia involving lymph nodes), 8 expressed B-cell markers, 2 expressed both T and B-cell markers.

CONCLUSIONSFlow cytometry can demonstrate aberrant antigen expression in lymphoma/leukemia cells and is helpful in delineating their cell origin. The technique is thus useful in the differential diagnosis of lymphoma/leukemia.

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; CD13 Antigens ; metabolism ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; CD79 Antigens ; metabolism ; Diagnosis, Differential ; Flow Cytometry ; Humans ; Leukemia, B-Cell ; diagnosis ; immunology ; Leukemia, T-Cell ; diagnosis ; immunology ; Lymphoma, Mantle-Cell ; diagnosis ; immunology ; Peroxidase ; metabolism ; Retrospective Studies ; Sialic Acid Binding Ig-like Lectin 3

Mantle cell lymphoma, blastoid variant (B-MCL), is a very rare type of non-Hodgkin 's lymphoma exhibiting an aggressive clinical course. We describe a case of B-MCL showing generalized lymphadenopathy and leukemic conversion in a 62-yr-old man. The case was diagnosed and subclassified as B-MCL on the basis of cyto-morphology and immunophenotype. Microscopic examination of the peripheral blood (PB) showed a spectrum of cells ranging from small mature lymphocytes to medium- and large-sized lymphocytes with blast-like chromatin and prominent nucleoli. The lymphoma cells were monoclonal B cells with moderately intense surface IgM. They were CD5 positive, cyclin D1 positive, CD10 negative, and CD23 negative. The flow cytometric immunophenotyping and DNA ploidy analysis of the PB and material obtained by aspiration cytology supported the diagnosis of B-MCL. These findings underline the utility of aspiration cytology in diagnosing B-MCL when cytomorphologic examination is combined with flow cytometric analysis of immuno-phenotype and demonstration of proliferation markers.
Biological Markers ; Biopsy, Needle ; Cell Division ; Flow Cytometry ; Gene Rearrangement ; Humans ; Immunophenotyping ; Lymph Nodes/pathology ; Lymphoma, Mantle-Cell/*diagnosis/genetics/immunology/pathology ; Male ; Middle Aged