scholarly journals Pre-B cells in peripheral blood of multiple myeloma patients

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 416-422 ◽  
Author(s):  
LM Pilarski ◽  
MJ Mant ◽  
BA Ruether
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Peanut Agglutinin ◽  
Surface Phenotype ◽  
Large Pool ◽  
Hla Dr ◽  
B And T Lymphocytes

Abstract Although multiple myeloma is a disease of plasma cells, abnormalities have been detected in both B and T lymphocytes in peripheral blood. Although multiple myeloma patients are deficient in surface Ig (sIg)- positive B lymphocytes, analysis of lymphocytes present in blood indicates an abnormally large pool of circulating pre-B cells. These pre-B cells express BA-1, do not bear sIg, and contain cytoplasmic mu chains. High numbers of pre-B cells occur in 88% of individuals with frank myeloma and in 44% of individuals with monoclonal gammopathy of undetermined significance. Pre-B cells bearing BA-1 differ between patients in their expression of HLA-DR and receptors for peanut agglutinin (PNA). Those pre-B cells in myeloma patients are either BA- 1+ PNA- HLA-DR+ (54% of patients) or BA-1+ PNA+ HLA-DR- (30% of patients), or have a mixture of phenotypes (14% of patients). Pre-B cells of the PNA- phenotype are almost always HLA-DR+, and PNA+ pre-B cells are HLA-DR-. Within the same patient, the pre-B cell population varies by both quantitative and qualitative definitions. The number of pre-B cells may increase 460-fold and temporal shifts of surface phenotype from BA-1+ PNA- to BA-1+ PNA+ or vice versa have been detected. These observations indicate an abnormality in the B lymphocyte differentiation pathway leading to pre-B cells in the periphery that vary in number and cell surface phenotype, and that are unable to express sIg.

scholarly journals Pre-B cells in peripheral blood of multiple myeloma patients

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 416-422 ◽  
Author(s):  
LM Pilarski ◽  
MJ Mant ◽  
BA Ruether
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Peanut Agglutinin ◽  
Surface Phenotype ◽  
Large Pool ◽  
Hla Dr ◽  
B And T Lymphocytes

Although multiple myeloma is a disease of plasma cells, abnormalities have been detected in both B and T lymphocytes in peripheral blood. Although multiple myeloma patients are deficient in surface Ig (sIg)- positive B lymphocytes, analysis of lymphocytes present in blood indicates an abnormally large pool of circulating pre-B cells. These pre-B cells express BA-1, do not bear sIg, and contain cytoplasmic mu chains. High numbers of pre-B cells occur in 88% of individuals with frank myeloma and in 44% of individuals with monoclonal gammopathy of undetermined significance. Pre-B cells bearing BA-1 differ between patients in their expression of HLA-DR and receptors for peanut agglutinin (PNA). Those pre-B cells in myeloma patients are either BA- 1+ PNA- HLA-DR+ (54% of patients) or BA-1+ PNA+ HLA-DR- (30% of patients), or have a mixture of phenotypes (14% of patients). Pre-B cells of the PNA- phenotype are almost always HLA-DR+, and PNA+ pre-B cells are HLA-DR-. Within the same patient, the pre-B cell population varies by both quantitative and qualitative definitions. The number of pre-B cells may increase 460-fold and temporal shifts of surface phenotype from BA-1+ PNA- to BA-1+ PNA+ or vice versa have been detected. These observations indicate an abnormality in the B lymphocyte differentiation pathway leading to pre-B cells in the periphery that vary in number and cell surface phenotype, and that are unable to express sIg.

scholarly journals Myeloidderived peripheral blood suppressor cells at haematopoietic stem cell mobilisation in multiple myeloma patients

2021 ◽  
Vol 66 (2) ◽  
pp. 218-230
Author(s):  
T. A. Aristova ◽  
E. V. Batorov ◽  
V. V. Sergeevicheva ◽  
S. A. Sizikova ◽  
G. Yu. Ushakova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Suppressor Cells ◽  
Complete Response ◽  
Haematopoietic Stem Cell ◽  
Hla Dr ◽  
Healthy Donors

Introduction. Multiple myeloma (MM) is a B-cell malignancy with clonal expansion of plasma cells in bone marrow. Highdose chemotherapy with autologous haematopoietic stem cell transplantation is among main consolidation therapies in MM. Myeloid-derived suppressor cells (MDSCs) are immature myeloid-accompanying cells able to suppress the immune response. The administration of granulocyte colony stimulating factor (G-CSF) to mobilise haematopoietic stem cells (HSCs) increases the MDSC count in peripheral blood (PB).Aim — to study MDSC subsets in PB of remission MM patients and their incidence dynamics at HSC mobilisation.Methods. The study surveyed 35 MM patients prior to and after HSC mobilisation. The counts of granulocytic (G-MDSCs; Lin–HLA-DR–CD33+ CD66b+), monocytic (М-MDSCs; CD14+ HLA-DRlow/–) and early MDSCs (E-MDSCs; Lin–HLA-DR– CD33+ CD66b–) were estimated in flow cytometry.Results. Remission MM patients differed from healthy donors in higher relative counts of G-MDSCs (Lin–HLA-DR– CD33+ CD66b+) and increased relative and absolute counts of М-MDSCs (CD14+ HLA-DRlow/–). М-MDSCs significantly outnumbered G-MDSCs. MDSC subset counts were elevated in complete response (CR) and very good partial response (VGPR), as well as in partial response (PR). Higher relative MDSC counts were associated with greater pretreatment (2–3 lines of chemotherapy). After HSC mobilisation with cyclophosphamide 2–4 g/m2 + G-CSF (filgrastim 5 μg/kg/day), the median relative E-MDSC and M-MDSC counts increased by 2.3 and 2.0 times, respectively, while the relative G-MDSC count raised 46-fold perturbing the MDSC subset balance.Conclusion. Remission MM patients had the increased relative G-MDSC and both relative and absolute M-MDSC counts compared to donors. A greater patient pretreatment was associated with higher relative G-MDSC counts. Treatment response (CR/VGPR vs. PR) was not coupled with MDSC count variation. The G-CSF-induced HSC mobilisation entailed a significant expansion of all three MDSC subsets in PB.

scholarly journals Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1550-1553 ◽  
Author(s):  
J Berenson ◽  
R Wong ◽  
K Kim ◽  
N Brown ◽  
A Lichtenstein
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Peripheral Blood Lymphocytes ◽  
Immunoglobulin Gene

Because there is controversy regarding whether subsets of peripheral blood lymphocytes (PBLs) are part of the malignant clone in patients with multiple myeloma, we studied this question by immunoglobulin and T cell receptor gene analysis. Southern blot analysis with antibody probes demonstrated clonal immunoglobulin gene rearrangements in PBLs of seven of nine patients that were identical to those seen in their marrow plasma cells. Circulating plasma cells were not detected in any of these patients. In contrast, no patient demonstrated clonally rearranged T cell receptor genes. In one sequentially studied patient, PBLs obtained at diagnosis when he had stage I (Durie-Salmon) contained only germline DNA, while analysis of PBLs at relapse (stage III) revealed a clonally rearranged band. These data confirm the notion that circulating lymphocytes in patients with myeloma are part of the malignant clone and, furthermore, these malignant cells are of B cell rather than T cell lineage.

In Multiple Myeloma, Clonal Cells Are Unevenly Distributed among Peripheral Blood B Cell Subpopulations.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1426-1426
Author(s):  
Stefanos I. Papadhimitriou ◽  
Ioanna Gligori ◽  
Elpiniki Kritikou-Griva ◽  
Georgios Gortzolidis ◽  
Aggeliki Davea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
In Situ Hybridisation ◽  
Current Evidence ◽  
Chain Gene ◽  
Virtual Absence ◽  
Lineage Differentiation

Abstract BACKGROUND: Current evidence supports the existence of circulating clonal B cells in Multiple Myeloma (MM). However, attempts to enumerate and phenotypically characterise them have so far provided inconsistent results. Most investigators have studied unselected peripheral blood (PB) mononuclear cells, among which the clonal ones make only a small minority. Moreover, in most cases, numerical chromosomal changes were employed as a clonal marker, but aneuploidy is considered a late event in myelomagenesis. To overcome these difficulties, we have followed an alternative approach, by studying purified PB B cells and focusing on chromosomal translocations involving the immunoglobulin heavy chain gene (IGH) on region 14q32, a frequent, early and possibly crucial pathogenetic event in MM. METHODS: The study included 33 MM patients with 14q32 rearrangements, detected by conventional cytogenetics or florescence in-situ hybridisation (FISH) in the bone marrow at diagnosis. PB CD19+ cells were immunomagnetically isolated (>99% purity) and cytocentrifuged on slides. The slides were studied with a FICTION technique, ie a combination of FISH using a “break-apart” IGH probe set (Vysis Inc, Downers Grove, Il, USA) and indirect immunofluorescence for CD34, CD5, CD10, CD23 and CD38. To avoid the possibility of contaminating plasma cells, isolates with >1% CD19+CD38+++ cells on flow cytometry were excluded from FICTION study. RESULTS: “Positive” cells above the cutoff level of false positivity (4%) were detected in 25 cases (75.7%), ranging from 4% to 33% (median 9%) among the total CD19+ population. These cells were found to consistently express CD10 (83% to 100%, median 96%) and CD38 (79% to 100%, median 89%). They less commonly expressed CD23 (39% to 67%, median 46%) and very rarely CD34 (0% to 5%, median 0%) and CD5 (0% to 3%, median 0%). CONCLUSIONS: Our data suggest that circulating cells bearing IGH rearrangements are the rule in MM, making a small but detectable fraction of CD19+ cells. There mmunophenotypic profile supports the concept that clonal B cells represent advanced ontogenetic rather than early stages in B lineage differentiation. Finally, the virtual absence of CD5+ clonal cells is in accord with the view that the high number of PB CD5+ B cells in MM reflects an immunoregulatory network and does not result from clonal expansion.

scholarly journals A novel membrane antigen selectively expressed on terminally differentiated human B cells

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1922-1930 ◽  
Author(s):  
T Goto ◽  
SJ Kennel ◽  
M Abe ◽  
M Takishita ◽  
M Kosaka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Affinity Constant ◽  
Target Antigen ◽  
Specific Marker

Abstract A monoclonal antibody (MoAb) that defines a novel terminal B-cell- restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenstrom's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig- secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non- plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

scholarly journals A novel membrane antigen selectively expressed on terminally differentiated human B cells

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1922-1930 ◽  
Author(s):  
T Goto ◽  
SJ Kennel ◽  
M Abe ◽  
M Takishita ◽  
M Kosaka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Affinity Constant ◽  
Target Antigen ◽  
Specific Marker

A monoclonal antibody (MoAb) that defines a novel terminal B-cell- restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenstrom's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig- secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non- plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Monitoring of Dendritic Cell Numbers in Patients during the Treatment of Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5096-5096
Author(s):  
Lucie Kovarova ◽  
Roman Hajek ◽  
Adam Svobodnik ◽  
Miroslav Penka ◽  
Jiri Mayer
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cells ◽  
Dendritic Cell ◽  
Healthy Volunteers ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Initial Values ◽  
Hla Dr ◽  
Significant Difference

Abstract Objective: In this study, the proportion of dendritic cell (DC) subsets (myeloid DC1 and plasmacytoid DC2), T cells, B cells and NK cells was evaluated in peripheral blood of patients with multiple myeloma (MM) before and during treatment including autologous transplantation. Also control group of healthy volunteers was evaluated. Methods: Flow cytometric determination of relative cells number in unmanipulated peripheral blood was based on expression of the surface antigen: T cells (CD3/CD4/CD8), B cells (CD19/CD20), NK cells (CD3/CD16/CD56) and DC (CD83/HLA-DR/CD11c and CD83/HLA-DR/CD123). Results: Significant difference (p<0.01) was found in initial values of CD83+ cells between the group of healthy volunteers (n = 15; mean count of CD83+ cells 0,26 ± 0,15%; ratio DC1/DC2 = 1,54) and the group of patients before treatment (n = 15; 0,15 ± 0,03% CD83+; DC1/DC2 = 4,55). After induction treatment with VAD regimen (vincristine, adriamycin, dexamethasone) in a group of patients was the mean percentage of DC higher (0,18 ± 0,04% CD83+ cells; DC1/DC2 = 4,77) than initial values. Administration of G-CSF again increased the total DC numbers (0,34 ± 0,11%; DC1/DC2 = 2,3) and intermediate levels of DC counts were found in the apheresis products (0,22 ± 0,05%; DC1/DC2 = 1,21). After engraftment there were found the highest relative DC numbers (0,50 ± 0,21%; DC1/DC2 = 1,85) in patients. Within six months after transplantation were achieved pretreatment DC values when compared with DC values of healthy volunteers (p<0,97) (0,24 ± 0,08%; DC1/DC2 = 1,57). Total numbers of T cells did not significantly differ during treatment only the reverse CD4/CD8 ratio was found in majority of patients within six month after the transplantation. Conclusions: Untreated patients with MM have significant lower relative numbers of peripheral blood DC in comparison with healthy volunteers. The highest number of total DC was found after engraftment. The ratio DC1/DC2 showed relative majority of DC1 subtype and its the lowest value was found in the apheresis products. Normal DC values comparable with DC values of healthy volunteers were found in patients within six months after transplantation together with the reverse CD4/CD8 ratio.

scholarly journals Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1550-1553 ◽  
Author(s):  
J Berenson ◽  
R Wong ◽  
K Kim ◽  
N Brown ◽  
A Lichtenstein
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Peripheral Blood Lymphocytes ◽  
Immunoglobulin Gene

Abstract Because there is controversy regarding whether subsets of peripheral blood lymphocytes (PBLs) are part of the malignant clone in patients with multiple myeloma, we studied this question by immunoglobulin and T cell receptor gene analysis. Southern blot analysis with antibody probes demonstrated clonal immunoglobulin gene rearrangements in PBLs of seven of nine patients that were identical to those seen in their marrow plasma cells. Circulating plasma cells were not detected in any of these patients. In contrast, no patient demonstrated clonally rearranged T cell receptor genes. In one sequentially studied patient, PBLs obtained at diagnosis when he had stage I (Durie-Salmon) contained only germline DNA, while analysis of PBLs at relapse (stage III) revealed a clonally rearranged band. These data confirm the notion that circulating lymphocytes in patients with myeloma are part of the malignant clone and, furthermore, these malignant cells are of B cell rather than T cell lineage.

scholarly journals Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1113-1122 ◽  
Author(s):  
Karin Tarte ◽  
John De Vos ◽  
Thomas Thykjaer ◽  
Fenghuang Zhan ◽  
Geneviève Fiol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Expression Profiles ◽  
Homogeneous Population ◽  
Normal Plasma

A new way to identify tumor-specific genes is to compare gene expression profiles between malignant cells and their autologous normal counterparts. In patients with multiple myeloma, a major plasma cell disorder, normal plasma cells are not easily attainable in vivo. We report here that in vitro differentiation of peripheral blood B lymphocytes, purified from healthy donors and from patients with multiple myeloma, makes it possible to obtain a homogeneous population of normal plasmablastic cells. These cells were identified by their morphology, phenotype, production of polyclonal immunoglobulins, and expression of major transcription factors involved in B-cell differentiation. Oligonucleotide microarray analysis shows that these polyclonal plasmablastic cells have a gene expression pattern close to that of normal bone marrow–derived plasma cells. Detailed analysis of genes statistically differentially expressed between normal and tumor plasma cells allows the identification of myeloma-specific genes, including oncogenes and genes coding for tumor antigens. These data should help to disclose the molecular mechanisms of myeloma pathogenesis and to define new therapeutic targets in this still fatal malignancy. In addition, the comparison of gene expression between plasmablastic cells and B cells provides a new and powerful tool to identify genes specifically involved in normal plasma cell differentiation.

scholarly journals High-dose sequential chemoradiotherapy in multiple myeloma: residual tumor cells are detectable in bone marrow and peripheral blood cell harvests and after autografting

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1596-1602 ◽  
Author(s):  
P Corradini ◽  
C Voena ◽  
M Astolfi ◽  
M Ladetto ◽  
C Tarella ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Disease Status ◽  
Residual Tumor ◽  
High Dose ◽  
Myeloma Cells ◽  
Igh Genes

Based on preliminary encouraging results in terms of response rate and survival, high-dose chemoradiotherapy has gained considerable interest in the treatment of patients with multiple myeloma (MM). We have evaluated the presence of residual myeloma cells in 15 of 18 patients enrolled in a high-dose sequential (HDS) chemoradiotherapy program followed by autografting. Our analysis has been performed both on bone marrow (BM) and peripheral blood (PB) cell harvests and after autografting. As it has been recently shown that B cells clonally related to malignant plasma cells are detectable in MM patients, we have developed a polymerase chain reaction (PCR)-based strategy to detect both residual B cells and plasma cells using clone-specific sequences derived from the rearrangement of Ig heavy chain (IgH) genes. The complementarity-determining regions (CDR) of IgH genes have been used to generate tumor-specific primers and probes. The constant (C) region usage defined the differentiation stage of residual myeloma cells. We report that plasma cells were detectable in PB and BM cell harvests and after transplantation in all assessable patients, irrespective of disease status. B cells were detectable in a consistent proportion of BM and PB samples at diagnosis, but only in one case at the time of PB and BM cell harvests. These cells became sometimes detectable after transplantation. Whether residual myeloma cells are clonogenic and contribute to relapse is currently unknown, and further investigations are required.

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