Expression patterns of CD200 and CD148 in leukemic B-cell chronic lymphoproliferative disorders and their potential value in differential diagnosis

2015 ◽  
Vol 56 (12) ◽  
pp. 3329-3335 ◽  
Author(s):  
Lei Fan ◽  
Yi Miao ◽  
Yu-Jie Wu ◽  
Yan Wang ◽  
Rui Guo ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
B Cell ◽  
Expression Patterns ◽  
Lymphoproliferative Disorders ◽  
Potential Value

Differential Diagnosis of Lymphoid Enhancer-Binding Factor 1 Between Chronic Lymphocytic Leukemia and Other B-Cell Chronic Lymphoproliferative Disorders

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4148-4148
Author(s):  
Lei Fan ◽  
Tingmei Shen ◽  
Rong Wang ◽  
Yi Miao ◽  
Yujie Wu ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Chronic Lymphocytic Leukemia ◽  
Protein Expression ◽  
B Cell ◽  
Mrna Expression ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Expression Level ◽  
Healthy Controls ◽  
Higher Sensitivity

Abstract Background : LEF1, lymphoid enhancer factor 1, is a key transcription factor of Wnt signaling pathways. In normal blood cells, the LEF1 mainly expresses in pre-B and T cells, involves in proliferation and differentiation. With mature of the cells, the expression of LEF1 reduces gradually. Its abnormal expression is associated with a variety of tumors, such as various kinds of leukemias and lymphomas. Previous studies have explored the relationship between LEF1 gene and tumorogenesis as well as tumor development, and there is little report on the diagnostic significance of LEF1. Recent studies have shown that the LEF1 protein expression in chronic lymphocytic leukemia (CLL) is significantly higher than other B-cell chronic lymphoproliferative disorders (B-CLPD) and normal controls. Our study aimed to compare the LEF1 gene mRNA expression and the LEF1 protein expression between different subtypes of patients with B-CLPD, then established the differential diagnostic value of LEF1 in B-CLPD. Methods: We determined the expression level of LEF1 protein by immunohistochemistry in bone marrow samples from 143 patients with leukemic phase B-CLPD including 78 cases of CLL, 17 cases of mantle cell lymphoma (MCL), 20 cases of Waldenström macroglobulinemia (WM), 20 cases of follicular lymphoma (FL), 5 cases of marginal zone lymphoma (MZL), 3 cases of B-cell chronic lymphoproliferative disorders-unclassified (B-CLPD-U). We used real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) to compare the level of LEF1 mRNA expression in malignant cells from 54 B-CLPD patients, including 44 cases of CLL, 3 cases of MCL, 2 cases of MZL, 3 cases of FL, one case of hairy cell leukemia (HCL), one case of B-cell prolymphocytic leukemia (B-PLL) and 5 cases of healthy donors. All statistical analysis of the data were performed using SPASS version 20.0. Mann-Whitney U test was used to compare the difference between the cohorts. P<0.05 was considered statistically significant. Results: The expression of LEF1 protein was positive in 68 of 78 patients with CLL and 2 of 20 patients with FL, both of whom were pathological low-grade. LEF1 expression of patients with WM, MCL, B-CLPD-U were all negative. The expression level of LEF1 protein in CLL was higher than other B-CLPD patients (including all FL, WM, MCL, B-CLPD-U, P=0.000). Positive expression of LEF1 protein can be used as novel differential diagnostic marker for patients with CLL with higher sensitivity and specificity (sensitivity=87%, specificity=97%).The expression of LEF1 protein was negative in 10 of 78 CLL patients. The 10 patients had atypical immunophenotype. The expression of CD20 was increased, even strong expression in 5 CLL patients. There were 9 CLL with CD200/CD148<1, and 6 cases with CD5 dim expression.The expression level of LEF1 gene in CLL patients was much higher than non-CLL patients and healthy controls (P=0.036, 0.004). The expression level of LEF1 gene had no statistical difference between non-CLL patients and healthy controls (P=0.438). The expression of LEF1 mRNA in 25% CLL patients was lower than healthy controls and 33.3% CLL patients was lower than non-CLL patients. Conclusions: The expression level of LEF1 protein was significantly higher than non-CLL in B-CLPD. We analyzed LEF1 protein may be a novel marker in the differential diagnosis of B-CLPD with higher sensitivity and specificity.The mRNA expression level of LEF1 gene in CLL patients was significant higher than non-CLL patients, but the expression of LEF1 mRNA in 25% CLL patients was lower than healthy controls and 33.3% CLL patients was lower than non-CLL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Quantitative flow cytometry for the differential diagnosis of leukemic B-cell chronic lymphoproliferative disorders

2000 ◽  
Vol 64 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Giovanni D'Arena ◽  
Pellegrino Musto ◽  
Nicola Cascavilla ◽  
Matteo Dell'Olio ◽  
Nicola Di Renzo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Differential Diagnosis ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Quantitative Flow

Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders

2003 ◽  
Vol 30 (2) ◽  
pp. 201-205 ◽  
Author(s):  
Gerassimos A. Pangalis ◽  
Marie-Christine Kyrtsonis ◽  
Flora N. Kontopidou ◽  
Theodoros P. Vassilakopoulos ◽  
Marina P. Siakantaris ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Low Grade ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

scholarly journals The role of immunophenotyping in differential diagnosis of chronic lymphocytic leukemia

2014 ◽  
Vol 142 (3-4) ◽  
pp. 197-203 ◽  
Author(s):  
Tijana Dragovic-Ivancevic ◽  
Nada Kraguljac-Kurtovic ◽  
Vesna Knezevic ◽  
Andrija Bogdanovic ◽  
Biljana Mihaljevic ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Differential Diagnosis ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
De Novo ◽  
Expression Patterns ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Very High Frequency ◽  
Marker Combination

Introduction. Accurate diagnosis of chronic lymphocytic leukemia (CLL) acquires immunophenotyping by flow cytometry in order to facilitate differential diagnosis between CLL and other mature B-cell neoplasms (MBCN). Objective. The aim of this study was to define immunological profile of CLL cells. Methods. Immunophenotyping by flow cytometry was performed on peripheral blood specimens at diagnosis in the group of 211 patients with de novo MBCN. Results. Absolute count of B-cells was significantly increased in all MBCN patients comparing to healthy control group (p<0.05). B-cell monoclonality was detected in 96% of all MBCN patients, by using surface immunoglobulin (sIg) light chain restriction. B-cell antigens, CD19, CD20, CD22, were expressed with very high frequency in CLL and other MBCN. In comparison with other MBCN, in CLL group, the frequency of expression was higher for CD5 and CD23 (p<0.0001), though lower for FMC7 antigen (p<0.0001). CLL patients were characterized by lower expression patterns of CD20, CD22, CD79b, and sIg (p<0.0001) as well as higher expression pattern of CD5 antigen (p<0.05). Correlation between the final diagnosis of MBCN and values of CLL scoring system showed that the majority of CLL patients (97%) had higher values (5 or 4) whereas the majority of other MBCN patients (96%) had lower score values (0-3). Conclusion. Our results have shown that characteristic immunophenotype which differentiates CLL from other MBCN is defined by following marker combination - CD19+ CD20+low CD22+low CD5+high CD23+ FMC7- CD79b+low sIg+low. CLL score values of 5 or 4 points are highly suggestive for diagnosis of CLL.

scholarly journals The Role of Molacular Genetic Examination in Differential Diagnosis and Prognostic Prediction in Patints with B-Cell Chronic Lymphoproliferative Disorders: A Restrospective Study of 1592 Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5329-5329
Author(s):  
Yuting Yan ◽  
Wenjie Xiong ◽  
Shuhua Yi ◽  
Li Zengjun ◽  
Dehui Zou ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Initial Time ◽  
Female Ratio ◽  
Male Predominance ◽  
Biopsy Specimens ◽  
Prognostic Prediction

Abstract Background: B-cell chronic lymphoproliferative disorders (BCLPD) are a heterogeneous group of mature B-cell malignancies characterized by monoclonal proliferation in the bone marrow (BM) or peripheral blood (PB). The overlapped clinical features and the lack of individual diagnostic markers make diagnosis challenging, especially in patients who have difficulty to get adequate non-BM biopsy specimens or patients manifest as leukemic onset without nodes-involvement. It is necessary to explore novel methods to make precise diagnostic classification and prognostic prediction through simply PB/BM examination. Methods and results: A total of 1592 patients with newly diagnosed BCLPD were enrolled from January 1998 to December 2016, of which chronic lymphocytic leukemia (CLL) accounted for 39%, leukemic marginal zone lymphoma (l-MZL)occupied 13%, and Waldenstrom's macroglobulinemia/ lymphoplasmacytic lymphoma (LPL/WM), leukemic follicular lymphoma (l-FL) and mantle cell lymphoma (l-MCL) were 13%, 9% and 8%, respectively. There are 14% patients failed to fit into any of the categories and remaining unclassified which defined as BCLPDU. The median age at diagnosis was 58 years old. The male/female ratio of all BCLPD patients was 1.84:1. Male predominance was pronounced in WM/LPL, l-MCL and HCL with a M/F ratio of 2.5-2.7, while with balance gender in l-MZL and l-FL. FISH analyses were performed in 1234 patients. 17p and 11q deletion were most common in l-MCL (36% and 17%), while 13q deletion and trisomy 12 were most frequent in CLL (35% and 21%). Patients with 17p deletion showed significantly adverse survival in CLL and l-MCL (p<0.05), but the phenomenon was not found in other types of BCLPD. Instead, complex karyotype showed better predictive capability of worse survival than 17p deletion in patients with l-FL, l-MZL and BCLPDU. A total of 665 patients had been successfully amplified the IGHV-IGHD-IGHJ rearrangements. Based on a cut-off value of 98% homology, the IGHV mutated proportion in patients with l-MCL was 48.6%, which was higher than other BCLPDs, following CLL 33.3% and l-MZL 28.6%, while most of WM and l-FL were unmutated. The most frequent rearrangement in l-MZL were IGHV1-2*01, which was seldom found in other subtypes. Also, DH2-2 and VH3-7 were mainly found in CLL and l-MCL respectively. Besides, we have identified several stereotyped IGH CDR3 which were specific for the certain BCLPD subtype. About 23% unclassified patients could acquire further diagnosis according to the special mutation status, VDJ rearrangements or stereotyped CDR3 sequencing. With a median follow-up of 50.3 months, 522 patients (38.0%) had disease progression or died. Patients with lMCL have a significant worse survival than other entities, with a 3-year overall survival (OS) rate of 58%. Following , patients with WM/LPL had relatively poorer prognosis with a 5-year OS rate of 68.2%, while the prognosis for l-MZL, l-FL and CLL were relatively favourable, with a 5-year OS of 80%.The OS of the B-CLPD had improved over time due to the emergence of immunotherapy and novel (3-year OS improved from 82.1% to 92.2%). The improvement of l-MCL and WM was obvious but not for CLL and l-MZL. Conclusion: Non-BM biopsy specimens are not available for part of BCLPD patients. Overlapped magnification of BM/PB brings on difficulties in differential diagnosis. Besides morphology and immunophenotype, comprehensive analysis of FISH, karyotype, IGHV, MYD88 or BRAF mutation and other molecular examination might contribute to further differential diagnosis and prognostic prediction. Moreover, it might provide advice for the initial time and strategy of treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Programmed Death-1 and Programmed Death-Ligand 1 Expression Patterns in Pediatric Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5316-5316
Author(s):  
Akihiro Tamura ◽  
Makiko Yoshida ◽  
Nobuyuki Yamamoto ◽  
Nanako Nino ◽  
Naoko Nakatani ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Small Proportion ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Pediatric Lymphoma ◽  
Programmed Death

Abstract Introduction The programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway is an inhibitory immune checkpoint that can suppress T-cell-mediated tumor cytotoxicity. Anti-PD-1 monoclonal antibodies have recently been recognized as promising therapy for adult patients with lymphoma, particularly in classical Hodgkin's lymphoma. However, little information is available regarding the expression patterns of PD-1 and PD-L1 in pediatric lymphoma. Therefore, this study aimed to investigate the expression patterns of PD-1 and PD-L1 in pediatric lymphoma. Methods Immunohistochemical analysis was performed on paraffin-embedded pretherapeutic tumor biopsies from 36 newly diagnosed pediatric patients (aged 0-15 years) with lymphoma or lymphoproliferative disorders treated at Kobe Children's Hospital (Kobe, Japan) from 2003 to 2018. Results Thirty-six samples comprising 11 of Burkitt lymphoma (BL), 7 of anaplastic large-cell lymphoma (ALCL), 6 of T-lymphoblastic lymphoma (T-LBL), 5 of diffuse large B-cell lymphoma (DLBCL), 3 of Hodgkin's lymphoma (HL), 2 of chronic active EBV-associated lymphoproliferative disorders (CAEBV-LPD), 1 of T cell/histiocyte rich B-cell lymphoma (T/HRBCL), and 1 of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) were evaluated. PD-L1 and PD-1 staining results in each lymphoma type are explained below and in Table. Burkitt lymphoma None of the 11 samples stained for PD-L1 or PD-1 in BL cells. PD-1 was expressed in a small proportion of tumor-infiltrating lymphocytes (TIL) in 3 of the 11 samples. Anaplastic large-cell lymphoma PD-L1 was robustly expressed in ALCL cells in 5 of the 7 samples. However, PD-1 was not expressed in any ALCL cell samples but expressed in a small proportion of TIL in only 1 sample. T-lymphoblastic lymphoma None of the 6 samples stained for PD-L1 in T-LBL cells. PD-1 was stained in T-LBL cells in only 1 sample. Moreover, PD-1 was not stained in TIL in any samples. Diffuse large B-cell lymphoma None of the 3 samples with DLBCL-not otherwise specified (DLBCL-NOS) or 1 sample with DLBCL with IRF4 rearrangement expressed PD-L1 on tumor cells. Conversely, PD-L1 was overexpressed in tumor cells in 1 sample with DLBCL with an interfollicular pattern of proliferation (DLBCL-IF). However, PD-1 was not expressed in any DLBCL cell samples. PD-1 was expressed in a small proportion of TIL in 1 sample with DLBCL with IRF4 rearrangement. Hodgkin's lymphoma PD-L1 was overexpressed in HL cells in both nodular sclerosis classic HL (NScHL), whereas PD-L1 was not expressed in nodular lymphocyte predominant HL (NLPHL) cells. PD-1 was not expressed in HScHL or NLPHL cells but was expressed in a small proportion of TIL in 1 sample with NLPHL. Chronic active EBV-associated lymphoproliferative disorders PD-L1 was overexpressed in tumor cells in both samples with CAEBV-LPD. PD-1 was not expressed in tumor cells but was expressed in a small proportion of TIL in 1 sample. T cell/histiocyte-rich B-cell lymphoma PD-L1 was overexpressed on tumor cells in T/HRBCL. PD-1 was weakly expressed in a part of T/HRBCL cells but strongly expressed in TIL. Subcutaneous panniculitis-like T cell lymphoma PD-L1 was overexpressed in tumor cells in SPTCL. However, PD-1 was not expressed in SPTCL cells or TIL. Discussion In this pediatric cohort, PD-L1 was overexpressed in tumor cells in ALCL (5/7), DLBCL-IF (1/1), NScHL (2/2), CAEBV-LPD (2/2), T/HRBCL (1/1), and SPTCL (1/1), but not in BL, T-LBL, DLBCL-NOS, or NLPHL. While the PD-L1 expression in EBV-positive lymphoma cells has been reported before, this study demonstrated the PD-L1 overexpression in CAEBV-LPD. In addition, we demonstrated the PD-L1 overexpression on SPTCL and DLBCL-IF cells, whereas the PD-L1 overexpression in T/HRBCL cells was consistent with previous reports. This study demonstrated that the PD-1 expression in tumor cells was rare in pediatric lymphoma. In addition, PD-1 expressions in TIL tended to be low in pediatric lymphoma, except for NLPHL and T/HRBCL. Besides classic HL, PD-1 blockade might be a promising treatment strategy for ALCL, DLBCL-IF, CAEBV-LPD, T/HRBCL, and SPTCL in children. Indeed, anectodal reports showed promising efficacy in ALCL. Therefore, further investigations are required to assess the role of the PD-1-PD-L1 pathway in pediatric lymphoma. Disclosures No relevant conflicts of interest to declare.

Lymphoproliferative disorders (LPD) involving lungs: T and B cell subsets within pulmonary infiltrates and in peripheral blood

1984 ◽  
Vol 42 ◽  
pp. 700-701
Author(s):  
Irene Stachura ◽  
Milton H. Dalbow ◽  
Michael J. Niemiec ◽  
Matias Pardo ◽  
Gurmukh Singh ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Mixed Population ◽  
Lymphoid Cells ◽  
Lymphomatoid Granulomatosis ◽  
Cell Type ◽  
Cell Surface Antigens ◽  
Pulmonary Infiltrates ◽  
B Cell Subsets

Lymphoid cells were analyzed within pulmonary infiltrates of six patients with lymphoproliferative disorders involving lungs by immunofluorescence and immunoperoxidase techniques utilizing monoclonal antibodies to cell surface antigens T11 (total T), T4 (inducer/helper T), T8 (cytotoxic/suppressor T) and B1 (B cells) and the antisera against heavy (G,A,M) and light (kappa, lambda) immunoglobulin chains. Three patients had pseudolymphoma, two patients had lymphoma and one patient had lymphomatoid granulomatosis.A mixed population of cells was present in tissue infiltrates from the three patients with pseudolymphoma, IgM-kappa producing cells constituted the main B cell type in one patient. In two patients with lymphoma pattern the infiltrates were composed exclusively of T4+ cells and IgG-lambda B cells predominated slightly in the patient with lymphomatoid granulomatosis.

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