Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The origin of the malignant stem cell in multiple myeloma, despite years of investigation by many laboratories, remains elusive. We have described a population of monoclonal circulating B-lineage lymphocytes that has been detected in all myeloma patients analyzed, both at diagnosis and after chemotherapy, and that has many properties consistent with its definition as either a stem cell compartment or an intermediate between the stem cell and the bone marrow localized plasma cells. On average, 40% to 50% of peripheral blood mononuclear cells are abnormal B cells that express CD10 and PCA-1 in conjunction with B-lineage markers CD19, CD20, and CD24 and variable expression of CD5. The B cells are monoclonal by Southern blot analysis and represent a highly pleiomorphic population. The migratory patterns of these cells are unknown, and their presence in blood may reflect cells in transit from a parent organ such as spleen to bone marrow for terminal differentiation, or they may originate in the bone marrow prior to circulation and seeding of other skeletal or extraskeletal sites. The working hypothesis underlying this work postulates that these abnormal B cells originate outside the marrow, giving rise to plasma cells only after migration to the bone marrow, which provides a microenvironment conducive to terminal plasma cell differentiation. Bone marrow plasma cells do not include an actively proliferating component and are terminally differentiated end stage cells. In contrast, the circulating abnormal B cells include proliferating cells and appear to be heterogeneous in differentiation stage. Analysis of CD45 isoform expression indicates a population continuously differentiating from a late B-cell stage through the early plasma cell stages to an end stage plasma cell. Quantitative and qualitative expression of CD45 has been shown to characterize B-cell development, with a high density of the CD45RA isoform on mature resting B cells, a transition to CD45R0 on activated B cells, and a gradual loss of total CD45, predominantly of the CD45R0 isoform, during plasma cell development until, on end stage plasma cells, all CD45 expression is lost. In myeloma patients, all of these B-cell stages are represented, with the least differentiated B cells occurring in blood, intermediate stages in both blood and marrow, the most differentiated B and/or plasma cells in the bone marrow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal circulating B cells in multiple myeloma. A continuously differentiating, possibly invasive, population as defined by expression of CD45 isoforms and adhesion molecules. 153 57

The pathologic, immunologic, and clinical features of five cases of B-zone small lymphocytic lymphoma (BZSLL), characterized by a nondestructive growth pattern with a selective and complete replacement of the B-zone areas of lymph nodes, were examined. These findings were compared with those of 13 cases of intermediate differentiated lymphoma/mantle zone lymphoma (ILL/MZL) and 20 cases of typical small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). B-zone SLL was characterized histologically by a deceptively benign pattern at a low magnification, the lymph node architecture being substantially preserved, in contrast to the ILL/MZL and SLL/CLL cases, in which complete effacement of the normal architecture usually could be observed. Moreover, in BZSLL the cellular population was rather uniform and lacked either a prolymphocytic component or the small-cleaved lymphoid cells often seen in SLL/CLL and ILL/MZL cases, respectively. The phenotypic profile of the BZSLL clonal cell population studied by the immunoperoxidase method and by single- and double-labeling flow cytometric analyses (SIg+, CD19+, CD20+, CD21+, CD22+, CD24+, CD35+, CD37+, CD74+, CD45+, CD45R+, MB2+, HLA-DR+, Leu-8+, CD9+/-, CDw75+/-, CD5-/+, CD23-/+, CD10-, FMC7-, PCA-1-, CD25-, CD38-, CD43-, CD3-) appeared to be fairly homogeneous and sufficiently distinct from that of ILL/MZL, based on the absence of FMC7 and CD38 molecules, and from that of SLL/CLL due to significantly stronger expression of SIgs (P less than .05), the higher reactivity with anti-CD9 and -CD22 antibodies (P less than .05), the lower reactivity with anti-CD5 and -CD23 antibodies (P less than .05), and the absence of CD25 determinants. Several clinical features of patients with BZSLL, including age group, advanced stage disease, and high frequency of bone marrow and peripheral blood involvement, were similar to those found in the other patients with ILL/MZL and SLL/CLL, but none of the BZSLL patients had an absolute lymphocyte count higher than 15.0 x 10(9)/L at presentation. Based on the architectural pattern, cytologic features, immunophenotypes, and hematologic findings, we conclude that BZSLL is an unusual variant of SLL that is primary in the lymph nodes and should be distinguished from ILL/MZL and CLL.
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PMID:B-zone small lymphocytic lymphoma: a morphologic, immunophenotypic, and clinical study with comparison to "well-differentiated" lymphocytic disorders. 156 46

We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.
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PMID:Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity". 165 17

Maturation of adult human bone marrow (BM) B cells is accompanied by the sequential acquisition and loss of characteristic cell surface antigens (Loken et al., Blood 70:1316). Little is known about these changes in fetal BM B cells. In order to compare fetal with adult B cell development, we performed three-color, flow cytometric analyses of cell surface antigens, as well as nuclear TdT staining, on lymphoid cells from fetal BM. Mononuclear cells isolated from fetal BM (18-22 weeks) were stained with combinations of antibodies against CD3, CD10, CD19, CD20, CD21, CD22, CD34, CD45, PCA-1, IgM, and HLA-DR. Analysis of six separate fetal BM specimens indicated that combinations of cell surface antigens were expressed on analogous populations in fetal and adult BM. Consistent with adult BM, greater than 95% of TdT+ cells within the CD10+ population were CD34+, whereas less than 5% were CD34-. This CD10+/CD34+/TdT+ population constituted 30-40% of the total B cell compartment, compared with 10% in adults. Quantitative changes in CD45 expression on fetal BM B cells defined three clear populations, as has been observed in adults. In striking contrast to adult BM, greater than 95% of CD19+ and greater than 95% of surface IgM+ cells were CD10+, indicating that CD10 is a pan-B cell antigen in fetal BM. Virtually no mature B cells expressing CD21, CD22, or PCA-1 were detected in fetal BM. Our results indicate a preponderance of immature phenotypes exist in the fetal BM B cell compartment. These immature cells can be grouped into three distinct populations, and probably correspond to expanded populations found less frequently in adult BM. This striking increase in the earliest identifiable stages of B cell ontogeny is consistent with an active expansion of cells destined to constitute the humoral immune system during fetal development.
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PMID:Multiparameter flow cytometric analysis of human fetal bone marrow B cells. 169 9

We have recently described a reproducible method whereby colonies containing cells that secrete immunoglobulin (Ig) can be grown from normal, human, adult bone marrow samples. The present report characterizes the cells that initiate these colonies. It is shown that all clonogenic cells express the CD19 surface antigen, as removal of these cells before plating in the B-cell colony assay abolished the subsequent growth of plaque-forming, B-lineage colonies. Cells from both the CD10+ and CD20+ B-lineage subpopulations initiated the growth of B-cell colonies, as removal of either subset resulted in a 50% reduction in the number of resulting B-cell colonies. The removal of activated B cells (CD23+), plasma cells (PCA-1+), or myeloid cells (CD13+) did not lead to a significant depletion in B-cell colony formation. Pre-B cells that were not yet committed to Ig light chain expression were also able to differentiate and proliferate into Ig-secreting colonies under the culture conditions used. Colonies initiated by these light chain uncommitted cells were distinguished using a replicate protein immunoblotting technique, which detects the simultaneous secretion of Ig kappa and Ig lambda from single colonies. These experiments provide evidence that the CD10 antigen is expressed on B-lineage cells before Ig light chain commitment, whereas CD20 is not. In conclusion, this B-cell colony assay provides a system for studying the differentiation of bone marrow-derived B cells and their precursors into Ig-secreting cells.
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PMID:B-lineage colonies from normal, human bone marrow are initiated by B cells and their progenitors. 170 6

The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage.
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PMID:Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. 183 May

A human plasma cell leukaemia cell line (HSM-2) and a subclone (HSM-2.3) have been established from the bone marrow of a patient with bi-phenotypic leukaemia. Proliferation assays using a variety of cytokines demonstrated that HSM-2 proliferated in response to recombinant interleukin-6 (rIL-6), but did not respond to rIL-1, rIL-2, rIL-3, rIL-4, rIL-5, recombinant granulocyte-colony stimulating factor (rG-CSF), or recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF), and that HSM-2.3 responded to rIL-3 and rIL-6. HSM-2 expressed the CD38 (OKT10), PCA-1, cytoplasmic-IgM, and surface kappa light chain. HSM-2.3 expressed the CD14 (My4), CD33 (My9), CD38 (OKT10), CD19 (B4), CD24 (OKB2), CD10 (J5), PCA-1. HSM-2 and HSM-2.3 are useful tools for analysing the possible role of IL-3 and IL-6 in the oncogenesis of plasma cell leukaemia.
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PMID:Establishment and characterization of a plasma cell leukaemia cell line dependent for growth on IL-6 and a bi-phenotypic subclone dependent upon both IL-3 and IL-6. 206 60

15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B-cell phenotype different from that of B-CLL was observed (CD10-, CD19+, CD20+, CD21-, CD22+, CD37+, CD38-, FMC7+, LN1+, PCA-1+, BLy7+ and CD5-). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B-cell leukemias, which is closer to the plasma cell stage of differentiation than that of B-CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL.
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PMID:Immunophenotype of hairy-cell leukemia. 222 30

Immunophenotypic analyses of immature stage (day 19-23), intermediate stage (day 28-32), mature stage (day 34-37), and older stage (day 42-44) human hemopoietic mast cells from colonies grown in semi-solid agar cultures were performed to study the ontogeny and identity of this cell type and its relationship to other leukocytes. Intermediate to mature stage mast cells were positive with the YB5.B8 mouse monoclonal antibody, (McAb) specific for human mast cells, whereas the reactivity of immature mast cells with this McAb was inconsistent and older cells were generally negative. Mast cells at all stages of maturation were strongly positive for IgE receptor sites and negative with the Bsp-1 McAb, specific for human basophils. Mast cells at all stages of maturation were also strongly positive with the monocyte McAbs RPA-M1 (CD11), positive with the monocyte McAb OKM5 and the monocyte/granulocyte McAbs BMA-210 and MY7 (CD13), strongly positive with the B-cell markers J5 (CD10) and anti-IgM, and positive with the plasma cell marker PCA-1 and to a lesser extent with the activated B-cell marker CD23. The mast cells were also strongly positive with anti-CD45 to the common leukocyte antigen and positive with an antibody to HLA-DR and an antibody to FVIIIC. They were negative for specific T-cell markers. The diversity of this phenotype supports the current concept that mast cells originate from the pluripotential progenitor cells in the bone marrow.
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PMID:Immunophenotypic analyses of cultured hemopoietic mast cells. 239 49

Using a serum-free defined medium, we have established a human cell line, NCI-H929, from a malignant effusion occurring in a patient with IgAk myeloma. The cultured cells have the morphologic, ultrastructural, biochemical, immunologic, and cytochemical features of plasma cells. The cells have rearranged alpha and kappa genes and synthesize and secrete high amounts of IgAk (greater than 80 micrograms/10(6) cells per 24 hours). The cells express surface immunoglobulin (alpha and kappa), the plasma cell antigen PCA-1, the transferrin receptor (T9) and T10 but lack antigens associated with earlier stages of B cell development (HLA-DR, B1, B2, B4, CALLA), as well as other leukocyte-macrophage antigens and Epstein-Barr virus (EBV) nuclear antigen. Although molecular studies confirm that both the tumor and cultured cells are derived from the same clone of malignant B cells, the tumor cells were predominantly near-diploid, whereas the cultured cells are predominantly near-tetraploid with six copies of chromosome 8, four to six of which have an 8q + abnormality. However, both the tumor and the cultured cells have a rearrangement of the cellular c-myc proto-oncogene (located at 8q24) and express c-myc RNA. Although a modest number of human "plasmacytoid" cell lines have been established, most are lymphoblastoid lines lacking plasma cell features, while others appear to be early secretory cells. In contrast, NCI-H929 is a differentiated, highly secretory human plasma cell line.
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PMID:Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene. 242 57


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