Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.
 ...
PMID:Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients. 128 35

The phenotypic expression of Russell bodies (RB) in the tumor cells of two patients with different types of B-cell lymphoma and of one patient with plasma cell myeloma were examined. In both B-cell lymphomas, the RBs reacted consistently with anti-Leu 8 and anti-immunoglobulin M. The RBs in one case also reacted with other monoclonal antibodies, including anti-CD5, CD19, CD22, and CD25. The membranes of most of the tumor cells containing RBs did not stain. In the myeloma, the RBs reacted only with anti-immunoglobulin, and the myeloma cells expressed no surface antigens associated with B lymphocytes. This finding suggests that RBs do not form in cells that can transport glycoproteins to the cell membrane, but rather occur as a result of defective transport or process of certain glycoproteins by plasmacytoid cells.
 ...
PMID:Russell bodies consist of heterogenous glycoproteins in B-cell lymphoma cells. 131 69

Immunosuppression of immunoglobulin synthesis seen in patients with multiple myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year longitudinal study of an IgA-deficient blood donor who developed multiple myeloma, the presence of immunosuppressive CD5 positive B cells and T cells preceded the diagnosis of overt multiple myeloma and the appearance of immunosuppressive monocytes. These data argue that certain immune defects may be involved in the development of myeloma and are not simply a consequence of overt malignancy.
 ...
PMID:Abnormalities in immune regulation precede the development of multiple myeloma. 137 58

Because B lymphocytes bearing the CD5 antigen have been involved in many B-cell malignancies, we have investigated the presence of the CD5 B-cell antigen on B and plasma cells in monoclonal gammopathy. Quantification of CD5 B cells was made in the peripheral blood of seven individuals with monoclonal gammopathy of undetermined significance (MGUS) and in that of 21 patients with multiple myeloma (MM). The bone marrow of ten patients with MM was also studied. Patients with progressive MM presented a significant reduction in both B and CD5 B lymphocytes (i.e., percentages and absolute numbers), when compared with individuals with MGUS and patients with stable MM. These latter individuals and patients did not differ from healthy donors. No CD5 B cells were found in the bone marrow of patients with MM. Moreover, no CD5 antigen could be detected on eight freshly established human myeloma cells lines including six totally dependent on interleukin-6. However, it was weakly expressed on two standard myeloma cell lines not requiring exogenous interleukin-6 (i.e., RPMI 8226 and U 266). In conclusion, our data show mainly an overall reduction of the polyclonal CD5 B lymphocytes similar to what is observed for the other polyclonal B lymphocytes in patients with active MM. Finally, the expression of the CD5 antigen human myeloma cell lines is not constant.
 ...
PMID:CD5 B lymphocyte antigen in monoclonal gammopathy. 138 12

Peripheral blood cells of a patient with diffuse large cell non-Hodgkin's lymphoma presenting with hypereosinophilia were used to establish an EBV negative lymphoma cell line termed OCI-Ly17. Cells of the line stained positive for CD2 and CD5 determinants and demonstrated rearrangement of the T-cell receptor beta chain. The immunoglobulin heavy chain gene was found to be in germ line configuration. Northern blot studies using probes for IL-1 alpha, IL-3, IL-4, IL-5, IL-6, and GM-CSF showed message for IL-5 and IL-6. Supernatants of the cell line were evaluated on normal non-adherent, E-rosette depleted bone marrow cells to determine the presence of growth promoting activities for clonogenic eosinophilic progenitors. Eosinophilic colonies were observed. Their frequency depended upon the amount of supernatant added to the cultures. The growth promoting activity in the supernatant was reduced in a dose dependent manner by preincubation with increasing concentrations of anti-IL-5 antibodies. The supernatants of the cell line were also tested on the IL-6 sensitive human myeloma line OCI-My4 and myeloma colonies grew in response. This stimulatory activity within the supernatant was neutralized by addition of increasing concentrations of anti-IL-6 antibodies. Although producing IL-5 and IL-6 constitutively, the lymphoma line did not increase proliferation in response to either interleukin, nor did it show a reduced proliferative rate when antibodies to IL-5 or IL-6 were added to the cultures.
 ...
PMID:Constitutive production of the interleukins IL-5 and IL-6 by the lymphoma cell line OCI-Ly 17 derived from a patient with malignant lymphoma and hypereosinophilia. 149 76

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)
 ...
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 expression of both natural-killer (NK)-associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.
 ...
PMID:Increased expression of natural-killer-associated and activation antigens in multiple myeloma. 155 Jan 11

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.
 ...
PMID:Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity". 165 17

mAb to murine IL-5R were prepared by means of fusion between mouse myeloma cells and spleen cells from a rat immunized with membrane-enriched fractions of IL-5-dependent early B cell line (T88-M). Two mAb (H7 and T21) were selected for their competitive inhibition of receptor binding by 35S-labeled IL-5 and of IL-5 biologic activities. The number of binding sites recognized by the mAb on different cell lines correlated with IL-5 responsiveness. Most surface IgM+ peritoneal B cells were H7+ and more than 70% were also Ly-1(CD5)dull+, and responded to IL-5 for polyclonal IgM production in a high frequency. A significant proportion of splenic B cells reacted with these mAb, although lower number (one-log less) than peritoneal B cells and a small proportion of H7dull+ splenic B cells seems to be Ly-1(CD5)dull+, 1 of 200 splenic B cells responded to IL-5 for IgM production. These results suggest that IL-5R+ B cells may consist of a subpopulation of B cells. Intriguingly, lymphoid populations of bone marrow cells were stained with H7 and T21, whereas myeloid populations were brightly stained with only T21. Finally, both H7 and T21 mAb specifically precipitated a protein of a Mr 60,000 from 125I-labeled cell lysates of IL-5R+ T88-M cells. The IL-5R with similar size (Mr 55,000 to 60,000) was precipitated from the cell lysates of peritoneal B cells. T21 mAb but not H7 mAb precipitated a protein of a Mr 110,000 from the cell lysates of bone marrow cells.
 ...
PMID:Distribution of IL-5 receptor-positive B cells. Expression of IL-5 receptor on Ly-1(CD5)+ B cells. 169 59

A continuously growing, in vitro cell line with plasma cell characteristics has been established from the bone marrow of a patient with multiple myeloma. Surface marker characterization of the cells revealed a combination of markers normally associated with different developmental stages in the B cell lineage. The cell secretes immunoglobulin at a relatively low rate. The cell also expresses CD5 and secretes a factor which suppresses in vitro mitogen and antigen induced immunoglobulin synthesis by normal PBL.
 ...
PMID:Establishment and characterization of a CD5 positive, immunosuppressive human myeloma cell line. 170 Feb 38


1 2 3 4 5 6 Next >>