scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111 ◽  
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Abstract Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

scholarly journals The role of bone marrow microenvironment in the progression of multiple myeloma from monoclonal gammopathy of undetermined significance

2021 ◽  
Vol 16 (3) ◽  
pp. 26-32
Author(s):  
A. S. Khudovekova ◽  
Ya. A. Rudenko ◽  
A. E. Dorosevich
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Microenvironment ◽  
Genetic Mutations ◽  
Microbiome Composition ◽  
The Impact ◽  
Undetermined Significance

Multiple myeloma is a tumor of plasma cells, one of the most common malignant blood diseases. It is preceded by a stage called monoclonal gammopathy of undetermined significance, from which true multiple myeloma develops in only a small percentage of cases. It was assumed that this process is associated with the accumulation of genetic mutations, but in recent years there is increasing evidence that the bone marrow microenvironment plays a key role in progression and that it can become a target for therapy that prevents the myeloma development. The review considers the role of mesenchymal stem cells, immune system cells, endotheliocytes, fibroblasts, adipocytes, osteoclasts and osteoblasts in multiple myeloma progression, as well as the impact of the sympathetic nervous system and microbiome composition.

scholarly journals Characterization of Monoclonal Gammopathy of Undetermined Significance Progression to Multiple Myeloma through Meta-Analysis of GEO Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4395-4395
Author(s):  
Jihad Aljabban ◽  
David Chen ◽  
Francesca Cottini ◽  
Saad Syed ◽  
Nabeal Aljabban ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Signaling Pathways ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Upstream Regulators ◽  
Undetermined Significance

Background: Monoclonal gammopathy of undetermined significance (MGUS) is characterized by plasma cell production of abnormal monoclonal protein, or M protein. While MGUS itself is asymptomatic, it generally carries a 1% per year risk to progression to multiple myeloma (MM). The etiology of MGUS, as well as why it progresses to MM in some cases, remains unclear. Moreover, it is not known why some MGUS patients, such as African Americans, have higher risk to progression to MM. Contrasting MGUS and MM can potentially highlight genes that differentiate benign gammopathies from malignant ones and may be involved in disease progression from MGUS to MM. Methods: We employed our STARGEO platform to tag samples from the NCBI Gene Expression Omnibus and performed two separate meta-analysis to compare MGUS and MM transcriptomes. For the first meta-analysis, we tagged MGUS plasma cells recovered from the bone marrow of 101 patients and tagged plasma cells from 64 healthy subjects as a control. For the second analysis. We tagged CD138+ cells from the bone marrow of 383 MM patients and used the MGUS tagged samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis (IPA). Results: From our first meta-analysis of MGUS, we identified EIF2 signaling, regulation of EIF4 and p70S6K signaling, and JAK/STAT signaling as top canonical pathways. Top upstream regulators included TP53, TGFB1, and the proto-oncogene MYCN and MYC (with predicted activation). The most upregulated genes included pro-oncogenes such as KIT and MLLT3, which is well-studied in acute leukemia but not yet described in MGUS. Another top upregulated gene was NRG3, a myeloma growth factor. Additionally, our analysis highlighted key genes involved in transcription and epigenetic regulation. For example, there was upregulation of RBFOX2, which is involved in alternative splicing during oncogenesis and tumor progression, and of PARP15, a transcriptional repressor with poly(ADP-ribose) polymerase activity and candidate gene for drug targeting. Also, there was upregulation of the DNA damage-inducible gene GADD45A, found to promote global DNA methylation. Lastly, we found upregulation of COMMD3, a gene with a recently identified role in humoral activity and B cell migration. From our second meta-analysis comparing MM and MGUS directly, we identified mitochondrial dysfunction, oxidative phosphorylation, purine nucleotides de novo biosynthesis, and sirtuin signaling as top upstream regulators. Like our first analysis, TP53 (with predicted inhibition), TGFB1, and MYC (with predicted activation) were top upstream regulators. The most upregulated gene was NUP62, a nucleoporin and novel regulator of cell proliferation and inducer of MYC activity. Our analysis also illustrated pro-oncogenic signaling pathways such as the Wnt pathway through upregulation of the ubiquitin ligase RNF14 and serine/threonine kinase through upregulation of SRPK2. Moreover, we found upregulation of the super-enhancer DUSP4, a phosphatase whose over-activity may drive MM severity. Lastly, we found upregulation of lysosomal associated membrane protein LAMP5. LAMP5 was recently identified in single-cell RNA sequencing of MM patients and may play a significant role in disease. Conclusions: Our study illustrates signaling pathways in MGUS that are present in MM such as EIF2, JAK/STAT, and MYC signaling. We also illustrate gene activity in MGUS that may predispose to MM progression such as NRG3, RBFOX2, and PARP15. GADD45RA and COMMD3 may play novel roles in MGUS. Our second analysis highlighted disease activity that persist from MGUS to MM, such as MYC signaling. It is possible that the genes from this analysis that aims to distinguish MM from MGUS may be responsible for tipping the scales from benignity to malignancy. Genes such as DUSP4, RN14, LAMP5, and others could serve as novel biomarkers or targets to MM and risk of progression of MGUS to MM. Disclosures No relevant conflicts of interest to declare.

Pre Transplantation MGUS and Transformation to Multiple Myeloma in Kidney Transplantation: A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4779-4779
Author(s):  
Harris V.K. Naina ◽  
Robert Kyle ◽  
Thomas M. Habermann ◽  
Samar Harris ◽  
Fernando G. Cosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Kidney Transplantation ◽  
Renal Transplantation ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
M Protein ◽  
Biclonal Gammopathy ◽  
Undetermined Significance

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is reported in 3 to 5 percent of population, with the prevalence increasing with advancing age. Patients with MGUS are at increased risk for progression to multiple myeloma or other plasma cell dyscrasias. There is a paucity of information on clinical outcomes of patients with MGUS undergoing renal transplantation. A retrospective study was performed to determine wether MGUS is a contraindication to renal transplantation. Methods: Data was collected from both the kidney transplant and MGUS database. The diagnosis of MGUS was made on the basis of either serum protein electrophoresis (SPEP) or immunofixation after excluding multiple myeloma, amyloidosis and monoclonal immunoglobulin deposition disease. Results: Between 1977 and 2004, 3518 patients underwent kidney transplantation of whom 23 patients had a preexisting monoclonal gammopathy of undetermined significance (MGUS). Fourteen (61%) of these patients were males. The median age at the time of transplant was 59 ±12 years. Ten patients (43.5%) had IgG Kappa (GK), 7 (30.4%) had IgG Lambda (GL), 2 (8.7%) had IgA Lambda (AL), 1 (4.3%) had IgA Kappa (AK), 2 (8.7%) had IgM Lambda (ML). One patient had a biclonal gammopathy GL and ML. Patients were monitored with either SPEP or immunofixation for median duration of 1542 days after transplantation. Thirteen patients had either no change or stable monoclonal protein, 6 had a decrease in their paraprotein level. Two patients had a mild increase in their paraprotein. Two patients with GK developed into biclonal gammopathy (GK and AK). The median follow up of this cohort after the renal transplant was 1783 days. Twelve (52%) patients remained alive at the time of the study. A patient with GK prior to the transplant who underwent kidney transplantation twice developed a biclonal gammopathy and was found to have increased plasma cells (20%) in bone marrow after 14 years. On follow up for 6 years, his M-protein remained stable. Another patient was found to have 17% plasma cells around the time of kidney transplantation. He had a stable M-protein at follow-up, but underwent a stem cell transplant for recurrent immunotactoid glomerulonephritis. Two (9%) patients developed more than 15% plasma cells in their bone marrow with a stable M-protein. None of the patients with a preexisting MGUS evolved into multiple myeloma. Conclusion: In this small study, the presence of MGUS prior to kidney transplantation did not appear to have increased the incidence of multiple myeloma post transplant. Therefore, MGUS by itself should not be considered as an absolute contraindication for renal transplantation.

Double Hematological Malignancy: An Unusual Presentation in Three Cases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5294-5294
Author(s):  
Rami Y. Haddad ◽  
Navneet Attri ◽  
Yaser Kawar
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
B Cell ◽  
Hematological Malignancies ◽  
Plasma Cells ◽  
Hematological Malignancy ◽  
Lymphocytic Leukemia ◽  
Refractory Anemia

Abstract The occurrence of more than one hematological malignancy in the same patient is an unusual pathologic condition and may pose a difficult challenge during decision to start various chemotherapy regimens. Cases of solid tumors of lung and gastrointestinal tract have been noted secondary to treatment of hematological malignancies but the occurrence of two hematological malignancies concomitantly is a rare presentation. We describe three cases of coexistent hematological malignancies at our institution. First case describes a 77 yo male with synchronously occurring B cell Non Hodgkin Lymphoma: marginal zone lymphoma (main bone marrow population); Chronic Lymphocytic leukemia (Fluorescent-in–situ hybridization test positive for trisomy 12) and a Monoclonal Beta, elevated IgM, elevated B2. BM evaluation revealed involvement by both processes. The patient has been started on Rituximab recently. The second case is an 85 yo male with findings with peripheral blood flow cytometry consistent with chronic lymphocytic leukemia of B-cell immunophenotype and lymph node biopsy consistent with Follicular Lymphoma. He was found to be BCL2 + on BM and had a normal Karyotype: 46, XY. He was treated with Rituximab ×8 cycles. A follow up PET scan showed partial response. Our third case was an 83 yo man with simultaneous presentation of myelodysplastic syndrome (MDS) and multiple myeloma (MM). This patient had MDS (Refractory anemia with Ring sideroblasts RARS type) and smoldering Multiple myeloma (monoclonal plasma cells 10–15%) bone marrow infiltration which over a course of 3 years transformed into full blown Multiple Myeloma with bone marrow revealing 30–40% plasma cells and osteolytic lesions on skeletal survey. Cytogenetic were normal. He was treated with Lenalidomide (after failure of ESA) and became transfusion in dependent for one year (Hgb rose from baseline of 6–7 to 13 g/dL), after progression to active multiple myeloma he was treated with Thalidomide and Dexamthesone. He achieved a partial response on SPEP. Subsequently he was treated for MDS progression with Azacytidine for 5 cycles with minor hematological benefit (transfusion was less frequently), he recently succumbed to his disease, he was transfusion dependent and became acutely ill after an acute episode of diverticulitis. Patients with MM, MDS have been reported after chemotherapy but few cases documenting the coexistence of MDS and MM at diagnosis have been reported in the literature. Conclusion: In this report, we describe a three cases of double hematological clonal processes or malignancy, all diagnosed at same time, without preceding hematological disorder or chemotherapy, and all required treatment.

scholarly journals B-Cell Disorders and Curcumin

2015 ◽  
Vol 16 (3) ◽  
pp. 255-257 ◽  
Author(s):  
Terry Golombick ◽  
Terrence H. Diamond ◽  
Arumugam Manoharan ◽  
Rajeev Ramakrishna
Keyword(s):  
Multiple Myeloma ◽  
Early Intervention ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Studies ◽  
Monoclonal Gammopathy ◽  
Progressive Disease ◽  
Hematological Malignancies ◽  
Lymphocytic Leukemia ◽  
Undetermined Significance

Clinical studies with patients with early hematological malignancies (ie, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or stage 0/1 chronic lymphocytic leukemia) suggest that early intervention with curcumin, derived from the spice turmeric, may lead to prolonged survival and delay in progressive disease in some of these patients.

A Long-Term Study of Prognosis on Monoclonal Gammopathy of Undetermined Significance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4994-4994
Author(s):  
Delvyn Caedren Case ◽  
Marjorie A. Boyd
Keyword(s):  
Bone Marrow ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Long Term Study ◽  
Progression Of Disease ◽  
Undetermined Significance

Abstract From 1976 to 2006, 547 patients have been identified and followed for monoclonal gammopathy of undetermined significance (MGUS). Criteria of inclusion included presence of serum monoclonal protein of a concentration of 2 g per deciliter or less; no or moderate amounts of monoclonal light chains in the urine; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and proportion of plasma cells in the bone marrow of 5% or less. Patients identified as MGUS were followed every 6 months with physical examination, CBC, chemistries, and paraprotein studies. Ages ranged from 32 – 100 years (median 70 years). There were 214 males and 333 females. Over the 30 years of observation, 61 patients have developed disease progression: myeloma 29, lymphoma 12, macroglobulinemia 10, chronic lymphocytic leukemia 7, and amyloid 3. Time to develop myeloma ranged from 2–24 years (median 6 years), macroglobulinemia 2–8 years (median 5 years), and amyloid 3–10 years (median 10 years). Patients developed myeloma throughout the entire period of observation: 2, 3, 3, 4, 4, 4, 4, 5, 5, 5, 6, 6, 6, 6, 6, 7, 7, 8, 8, 9, 10, 10, 11, 14, 15, 15, 18, 20, and 24 years. Survival from diagnosis of myeloma was 1+ – 14+ months (median 36 months) for myeloma and 24 – 108+ months (median 48 months) for macroglobulinemia. The only reliable method of identifying progression of disease to myeloma/macroglobulinemia/amyloid was serial determinations of paraprotein level. In this large series followed for 30 years, with a more restricted diagnosis of MGUS (paraprotein level ≤ 2 g per deciliter and 5% or less bone marrow plasma cells), 1% of all patients identified developed progression of disease. No patient developed disease progression in less than 2 years using the more restricted diagnosis. Risk of progression increased with time with patients developing myeloma even 20 years or longer of follow-up. Serial evaluations of paraprotein levels are indicated in patients identified as MGUS.

Multiple Myeloma in Association With Sarcoidosis

2002 ◽  
Vol 126 (3) ◽  
pp. 365-368
Author(s):  
Filiz Şen ◽  
Karen P. Mann ◽  
L. Jeffrey Medeiros
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Aspiration ◽  
Bone Marrow Examination ◽  
Medical Attention ◽  
Non Hodgkin Lymphoma ◽  
Noncaseating Granulomas ◽  
Undetermined Significance

Abstract The association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G κ type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88–15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.

scholarly journals Distinct Nuclear Organization of Telomeresand Centromeres in Monoclonal Gammopathyof Undetermined Significance and Multiple Myeloma

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 723
Author(s):  
Yu ◽  
Wang ◽  
Tammur ◽  
Tamm ◽  
Punab ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Nuclear Organization ◽  
Precursor State ◽  
Structural Indicators ◽  
Disease Stages ◽  
Undetermined Significance

Both multiple myeloma (MM) and its precursor state of monoclonal gammopathy of undetermined significance (MGUS) are characterized by an infiltration of plasma cells into the bone marrow, but the mechanisms underlying the disease progression remain poorly understood. Previous research has indicated that 3D nuclear telomeric and centromeric organization may represent important structural indicators for numerous malignancies. Here we corroborate with previously noted differences in the 3D telomeric architecture and report that modifications in the nuclear distribution of centromeres may serve as a novel structural marker with potential to distinguish MM from MGUS. Our findings improve the current characterization of the two disease stages, providing two structural indicators that may become altered in the progression of MGUS to MM.

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