scholarly journals The basic study on kappa-lambda imaging by delta-curve for the detection of a monoclonal B-cell population in the peripheral blood

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1461-1466 ◽  
Author(s):  
M Nakano ◽  
S Kuge ◽  
S Kuwabara ◽  
M Yaguchi ◽  
Y Kawanishi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Basic Study ◽  
Minor Population ◽  
D Values ◽  
A Minor ◽  
D Value

Abstract Recently, kappa-lambda analysis with the “D” value was developed by Ault to detect a minor population of malignant B cells in peripheral blood. This analysis is based on the Kolmogorov-Smirnov test, and the D value is calculated by a flowcytometer and a computer. We have recently devised a more sensitive parameter for the kappa-lambda analysis than the D value called the delta-curve (delta c); the delta c applies the same principle as that of the D value. Mixing experiments with kappa- type and lambda-type chronic lymphocytic leukemia cells revealed that the delta c could not only detect a minor population of malignant kappa- B cells, but also that of malignant lambda-B cells using more sensitivity than the D value. A total of 49 blood samples obtained from 27 patients with various B-cell malignancies were investigated. D values were abnormal in 37% of all samples, while abnormal patterns of the delta c were recognized in 71%. On the other hand, 59% of samples obtained from the patients with B-cell lymphoma in aleukemic phase showed abnormal delta c, whereas D values exceeded the upper limit of the normal value in only 15% of the samples. It was suggested that the delta c could detect 3% to 7% of malignant B cells that were mixed with a population of normal lymphocytes.

scholarly journals The basic study on kappa-lambda imaging by delta-curve for the detection of a monoclonal B-cell population in the peripheral blood

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1461-1466
Author(s):  
M Nakano ◽  
S Kuge ◽  
S Kuwabara ◽  
M Yaguchi ◽  
Y Kawanishi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Basic Study ◽  
Minor Population ◽  
D Values ◽  
A Minor ◽  
D Value

Recently, kappa-lambda analysis with the “D” value was developed by Ault to detect a minor population of malignant B cells in peripheral blood. This analysis is based on the Kolmogorov-Smirnov test, and the D value is calculated by a flowcytometer and a computer. We have recently devised a more sensitive parameter for the kappa-lambda analysis than the D value called the delta-curve (delta c); the delta c applies the same principle as that of the D value. Mixing experiments with kappa- type and lambda-type chronic lymphocytic leukemia cells revealed that the delta c could not only detect a minor population of malignant kappa- B cells, but also that of malignant lambda-B cells using more sensitivity than the D value. A total of 49 blood samples obtained from 27 patients with various B-cell malignancies were investigated. D values were abnormal in 37% of all samples, while abnormal patterns of the delta c were recognized in 71%. On the other hand, 59% of samples obtained from the patients with B-cell lymphoma in aleukemic phase showed abnormal delta c, whereas D values exceeded the upper limit of the normal value in only 15% of the samples. It was suggested that the delta c could detect 3% to 7% of malignant B cells that were mixed with a population of normal lymphocytes.

scholarly journals A Tissue Counterpart to Monoclonal B-Cell Lymphocytosis

2021 ◽  
Author(s):  
Gabriel K. Habermehl ◽  
Lisa Durkin ◽  
Eric D. Hsi
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
High Count

Context.— B-cell clones discovered in tissue biopsies, without overt lymphoma, may represent a tissue counterpart to peripheral blood monoclonal B-cell lymphocytosis (MBL), herein termed tMBL. Objective.— To characterize the clinicopathologic features of tMBL. Design.— During a 10-year period, we retrospectively identified non–bone marrow/peripheral blood cases with monotypic B cells detected by tissue-based flow cytometry, but without an identifiable lymphomatous infiltrate on routine histopathology. We excluded cases with prior diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma or MBL. Results.— Fifty-four cases were identified (35 lymph node, 3 splenic, and 16 soft tissue/viscera). Forty-six cases were CLL-type, 2 were atypical CLL, and 6 were non-CLL. tMBL was detectable by immunohistochemistry in 14 cases (26%, all CLL-type). Concurrent blood flow cytometry, available in 10 cases, showed 4 with low-count MBL (3 CLL-type, 1 with non-CLL–type), 5 with high-count MBL (all CLL-type), and 1 case negative for clonal population. With median follow-up of 51 months, 2 patients had progression of disease (CLL, 68.7 months; and diffuse large B-cell lymphoma, 5.9 months). Patients with IHC-detectable tMBL had increased monoclonal B cells per total lymphocyte events (P = .01), morphologic evidence of bone marrow involvement (P = .04), higher white blood cell count (P = .02), and increased absolute lymphocyte count (P = .02). Conclusions.— tMBL spans an immunophenotypic spectrum similar to MBL, is detectable by immunohistochemistry in a minority of cases (often CLL immunophenotype), and is likely systemic in most cases. Development of overt lymphoma is uncommon but may occur, warranting clinical follow-up.

scholarly journals Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

2021 ◽  
Vol 12 ◽  
Author(s):  
Erwan Dumontet ◽  
Stéphane J. C. Mancini ◽  
Karin Tarte
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Niche Adaptation ◽  
Functional Features

B-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches.

Association between the proliferative rate of neoplastic B cells, their maturation stage, and underlying cytogenetic abnormalities in B-cell chronic lymphoproliferative disorders: analysis of a series of 432 patients

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 5130-5141 ◽  
Author(s):  
Sandra Quijano ◽  
Antonio López ◽  
Ana Rasillo ◽  
Susana Barrena ◽  
Maria Luz Sánchez ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Maturation Stage ◽  
Cytogenetic Abnormalities ◽  
M Phase ◽  
The Impact

Abstract Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B cells from chronic lymphoproliferative disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according to diagnosis and site of sampling, versus their normal counterparts. Overall, proliferation of neoplastic B cells highly varied among the different B-CLPD subtypes, the greatest numbers of proliferating cells being identified in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B cells, neoplastic B-CLPD cells showed significantly increased S + G2/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL, and some DLBCL cases. Conversely, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone, and MALT-lymphoma patients showed S + G2/M phase values similar to normal mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly higher percentages of S + G2/M cells were detected in BM versus PB and in LN versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene rearrangements and DNA aneuploidy, was associated with a higher percentage of S + G2/M-phase cells among LPL/WM and B-CLL cases, respectively.

scholarly journals Expression and release of CD27 in human B-cell malignancies

Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3430-3436 ◽  
Author(s):  
MH van Oers ◽  
ST Pals ◽  
LM Evers ◽  
CE van der Schoot ◽  
G Koopman ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Growth Factor Receptor ◽  
Lymphocytic Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
B Cell Malignancies ◽  
Variable Intensity ◽  
Hodgkin's Lymphomas

Abstract CD27, a transmembrane disulfide-linked 55-kD homodimer, belongs to the nerve growth factor-receptor family, a group of homologous molecules involved in lymphocyte differentiation and selection. It is expressed on mature thymocytes, peripheral blood T cells, and a subpopulation of B cells. We investigated the expression of CD27 on malignant B cells representative for a broad range of stages in physiologic antigen- independent and -dependent B-cell development. In normal lymphoid tissue CD27+ B cells were only found in the peripheral blood (29.8% +/- 10.8%, n = 13) and in germinal centers. With the exception of pro-B and the majority of pre-pre-B acute lymphocytic leukemias and of myelomas, CD27 expression of variable intensity was detected on almost all immature and mature malignant B cells tested. Moreover, using a sandwich enzyme-linked immunosorbent assay we could show the presence of sometimes very high (up to 6,000 U/mL; normal values < 190 U/mL) amounts of the soluble 28- to 32-kD form of CD27 (sCD27) in the sera of patients with B-cell malignancies. The highest levels of sCD27 were observed in patients with chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphomas. Most importantly, both in transversal and longitudinal studies, we found a strong correlation between sCD27 levels in the serum and tumor load, indicating that sCD27 can be used as a disease-marker in patients with acute and chronic B-cell malignancies.

scholarly journals Immunoglobulin secretory function of B cells from untreated patients with chronic lymphocytic leukemia and hypogammaglobulinemia: role of T cells

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 767-774 ◽  
Author(s):  
LA Fernandez ◽  
JM MacSween ◽  
GR Langley
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Cell Function ◽  
Lymphocytic Leukemia ◽  
Suppressor Activity ◽  
Normal Peripheral Blood

Abstract The mechanism of the hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) was studied by determining the generation of specific immunoglobulin-secreting cells in response to mitogen and antigen stimulation in culture. Normal peripheral blood B lymphocytes from 18 normal subjects cocultured with equal numbers of autologous T cells generated cells secreting 2,542 +/- 695 IgG, 2,153 +/- 615 IgA, and 2,918 +/- 945 IgM. Normal B lymphocytes cocultured with normal allogeneic T cells generated similar numbers. However, B lymphocytes from patients with chronic lymphocytic leukemia cocultured with T cells from the same patient generated only 0.5% as many cells secreting IgG and 11% and 23% as many secreting IgA and IgM, respectively. The reason for this markedly defective generation of immunoglobulin-secreting cells was investigated by evaluating T-helper, T-suppressor, and B-cell function using B cells from tonsil and T and B cells from peripheral blood of normal and leukemic individuals. T cells from patients with chronic lymphocytic leukemia provided somewhat greater help than did normal T cells to normal peripheral blood B cells and normal help to tonsil B cells, whether stimulated with mitogen or antigen. T cells from patients with chronic lymphocytic leukemia did not demonstrate increased suppressor function compared to normals with B cells from normal peripheral blood. The hypogammaglobulinemia in these patients therefore was associated with a markedly defective generation of immunoglobulin secreting cells, and as there was normal or increased T- cell helper activity without excessive suppressor activity, it seems likely that this was due to an intrinsic B-cell defect.

Increased Apoptosis of Peripheral Blood and Bone Marrow B and T Cells Correlates with Advanced Stages and Poor Risk Factors in Patients with B-CLL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4162-4162
Author(s):  
Malgorzata Sieklucka ◽  
Agnieszka Bojarska-Junak ◽  
Agata Surdacka ◽  
Iwona Hus ◽  
Ewa Wasik-Szczepanek ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Disease Progression ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Lymphocytic Leukemia ◽  
High Rate ◽  
Advanced Stage

Abstract B-cell chronic lymphocytic leukemia (B-CLL), is characterized by the accumulation of long-lived, neoplastic B-lymphocytes in peripheral blood, bone marrow and secondary lymphoid organs. Apoptotic processes have been shown to be altered in leukemic B cells, however, the role of apoptosis in the mechanisms of disease progression remains unclear. Recent studies suggest that the clonal excess of B-cells is caused not only by a decrease in cell death but also by increased cell proliferation. We have recently reported on a high rate of apoptosis leukemic B cells in peripheral blood (PB) of advanced stage patients and that apoptosis of PB lymphocytes from advanced-stage (III–IV acc. Rai) patients is higher than that in early-stage (0–II acc. Rai) patients. However the spontaneous apoptosis in B-CLL patients was significantly lower compared to the healthy controls that confirmed the defective apoptosis as one of the mechanisms of leukemic lymphocytes accumulation in B-CLL. Continuing our research, in the presented study we measured apoptosis of B and T cells in peripheral blood and bone marrow in correlation with the stage of B-CLL and prognostic factors. Materials and methods: Peripheral blood and bone marrow (BM) samples were obtained from 120 previously untreated B-CLL patients. An analysis of apoptosis within the B and T cells population was performed using flow cytometer and chloromethyl-X-rosamine staining (Mito Tracker Red CMXRos). CMXRos was used to detect disruptions in the mitochondrial membrane potential (ΔΨm), which is one of the earliest events in the apoptotic pathway and allow finding apoptotic cells when there are still in PB and BM. We found that ex vivo lymphocyte apoptosis was higher in BM compared to PB (p&lt;0.05). Moreover, both B-cell and T-cell apoptosis in BM was higher than in PB (p&lt;0.0001 and p&lt;0.001, respectively). When compared, ex vivo apoptosis of T cells was found higher than that of B cells, both in BM (p&lt;0.0001) and PB (p&lt;0.0001). The percentage of apoptotic leukemic B cells correlated negatively with Bcl-2/Bax ratio in CD19+ B cells (p&lt;0.05). Similarly, the percentage of apoptotic CD3+ cells correlated negatively with Bcl-2/Bax ratio in CD3+ cells (p&lt;0.01). We also found that the percentage of apoptotic leukemic B cells correlated positively with the expression of proapoptotic protein Par-4 (prostate apoptosis response-4) in CD19+ B cells (p&lt;0.01). The expression of Par-4 protein in CD19+ B cells correlated positively with the percentage of CD38+ cells (p&lt;0.05), and it was higher in patients with CD38+ and ZAP-70+/CD38+ phenotypes (p&lt;0.05 and p&lt;0.01, respectively). There was a positive correlation between the expression of Par-4 protein and the lactate dehydrogenase (LDH) and β2-microglobulin serum concentrations (p&lt;0.01 and p&lt;0.05, respectively). Furthermore, the percentage of apoptotic CD19+ cells correlated positively with the LDH serum level (p&lt;0.05). These data indicate that high amount of apoptotic leukemic cells in PB and BM might be considered as poor prognosis factor. Higher rate of B and T cells apoptosis in BM than in PB suggest the influence of bone marrow microenviroment on this process. Our results indicate also that high rate of T cells apoptosis might be responsible for immune dysfunction including both impaired anti-infection immunity as well as impaired anti-cancer response resulting in disease progression.

scholarly journals Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression

2016 ◽  
Vol 213 (13) ◽  
pp. 3007-3024 ◽  
Author(s):  
Kyoko Hayakawa ◽  
Anthony M. Formica ◽  
Joni Brill-Dashoff ◽  
Susan A. Shinton ◽  
Daiju Ichikawa ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Subset ◽  
Lymphocytic Leukemia ◽  
Transgenic Expression ◽  
Bcr Signaling ◽  
B Cell Subsets ◽  
A Minor ◽  
B1 B Cells

In mice, generation of autoreactive CD5+ B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from Eμ-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging. Increased anti-thymocyte/Thy-1 autoreactive (ATA) BCR cells in the B1 B cell subset by transgenic expression yielded spontaneous ATA B-CLL/lymphoma incidence, enhanced by TCL1 transgenesis. In contrast, ATA B-CLL did not develop from other B cell subsets, even when the identical ATA BCR was expressed on a Thy-1 low/null background. Thus, both a specific BCR and B1 B cell context were important for CLL progression. Neonatal B1 B cells and their CLL progeny in aged mice continued to express moderately up-regulated c-Myc and down-regulated proapoptotic Bmf, unlike most mature B cells in the adult. Thus, there is a genetic predisposition inherent in B-1 development generating restricted BCRs and self-renewal capacity, with both features contributing to potential for progression to CLL.

scholarly journals FTY720 demonstrates promising preclinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphoma

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 275-284 ◽  
Author(s):  
Qing Liu ◽  
Xiaobin Zhao ◽  
Frank Frissora ◽  
Yihui Ma ◽  
Ramasamy Santhanam ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Raji Cell ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Pp2a Activation

FTY720 is an immunosuppressant developed to prevent organ transplant rejection. Recent studies indicate an additional role for FTY720 in inducing cell apoptosis. We demonstrate here that FTY720 mediates toxic effects in cell lines representing different B-cell malignancies and primary B cells from patients with chronic lymphocytic leukemia (CLL). In contrast to previous reports in T-cell lines, FTY720-induced toxicity in the Raji cell line and primary CLL B cells is independent of activation of caspases or poly(ADP-ribose) polymerase processing. Further, pancaspase inhibitor Z-VAD-fmk failed to rescue these cells from apoptosis mediated by FTY720. FTY720 induced down-regulation of Mcl-1 but not Bcl-2 in CLL B cells. Overexpression of Bcl-2 failed to protect transformed B cells from FTY720-induced apoptosis, suggesting a Bcl-2–independent mechanism. Interestingly, FTY720 induced protein phosphatase 2a (PP2a) activation and downstream dephosphorylation of ERK1/2, whereas okadaic acid at concentrations that inhibited the FTY720-induced PP2a activation also resulted in inhibition of FTY720-mediated apoptosis and restoration of baseline ERK1/2 phosphorylation in primary CLL cells, indicating a role for PP2a activation in FTY720-induced cytotoxicity. Further, FTY720 treatment resulted in significant prolonged survival in a xenograft severe combined immunodeficiency (SCID) mouse model of disseminated B-cell lymphoma/leukemia. These results provide the first evidence for the potential use of FTY720 as a therapeutic agent in a variety of B-cell malignancies, including CLL.

scholarly journals Patterns of microRNA expression characterize stages of human B-cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4586-4594 ◽  
Author(s):  
Jenny Zhang ◽  
Dereje D. Jima ◽  
Cassandra Jacobs ◽  
Randy Fischer ◽  
Eva Gottwein ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Microrna Expression ◽  
Lymphocytic Leukemia ◽  
Cell Phenotype ◽  
Tumor Type ◽  
B Cell Differentiation ◽  
B Cell Malignancies

Abstract Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.

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