Expression of CD126 (IL-R alpha) on Plasma Cells in Monoclonal Gammopathies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5066-5066
Author(s):  
Syed T. Mahmood ◽  
Shaji Kumar ◽  
Teresa K. Kimlinger ◽  
Jessica L. Haug ◽  
Michael Timm ◽  
...  

Abstract Background: IL-6 is important for proliferation and inhibition of apoptosis in malignant plasma cells. Understanding the role of IL-6 receptor alpha chain (CD126) in the pathogenesis of plasma cell disorders may help in developing future treatment therapies for these diseases. A previous study has shown that CD126 (alpha subunit of IL-6 receptor) is expressed distinctly in myeloma, monoclonal gammopathy of unknown significance (MGUS), and plasmacytomas when compared to normal. We performed this study in order to confirm and describe the expression of CD126 in different plasma cell disorders. Design and Methods: Using flow cytometry we assessed CD126 expression on clonal plasma cells from patients with Primary Amyloidosis (n=7), monoclonal gammopathy of undetermined significance (MGUS) (n=13), smoldering Myeloma (SMM) (n=19) and active Myeloma (n=22), as well as normal plasma cells (n=9). Plasma cells were identified by their characteristic CD38/45 expression. The expression of CD126 was separately analyzed on the CD45 positive and negative plasma cells. CD 126 expression was considered significant when more than 20% of the cells had expression. Results: CD126 expression was seen distinctly in plasma cell disorder plasma cells and not in normal plasma cells when all plasma cells were studied together. The highest expression percentages were found in Amyloid (28%) followed closely by MGUS 29(%), then SMM (23%), and Myeloma (12%) cells. The CD45 neg subset was similarly positive in the plasma cell disorder group. In this group, MGUS showed the highest expression percentage followed distantly by Amyloid, Myeloma, and SMM. The CD45 pos subset was uniformly positive in expression of CD126. If was found that this subset expressed higher levels of CD126 in all the studied plasma cell disorders and normal plasma cells when compared to the CD45 neg subset. Conclusion: The findings of this study confirm the increased expression of CD126 in plasma cell disorders when compared to normal plasma cells. The higher expression of CD126 in the CD45 pos plasma cell subset has not been previously described. In addition, the CD45 pos subset expressed higher levels of CD126 in all study groups when compared to the CD45 pos subset. This data contributes to the understanding of IL-6 receptor physiology and confirms the important role of the CD45 pos subset in the proliferation of neoplastic plasma cells. The findings are in accordance with the increased proliferative rates seen in the CD45 fraction of malignant plasma cells.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5368-5368
Author(s):  
M Hasib Sidiqi ◽  
Mohammed A Aljama ◽  
David S. Viswanatha ◽  
David Dingli

Abstract T cell large granular lymphocytic (T-LGL) leukemia has been reported to occur in patients with plasma cell disorders (PCD). We conducted a retrospective review of patients diagnosed with T-LGL leukemia and a PCD at the Mayo Clinic. 22 patients were identified with T-LGL leukemia and a plasma cell disorder. The T-LGL leukemia preceded the PCD in 18% (n=4), was synchronous in 50% (n=11) and diagnosed post plasma cell disorder in 32% (n=7) of patients. The PCD diagnosis varied and included monoclonal gammopathy of undetermined significance (MGUS, n=13), multiple myeloma (MM, n=5), smoldering multiple myeloma (SMM. N=2), lymphoplasmacytic lymphoma (LPL, n=1) and monoclonal gammopathy of renal significance (MGRS, n=1). 5 patients developed T-LGL leukemia after treatment for a PCD (4 with MM and 1 with LPL). 4 patients with MGUS progressed to a more aggressive disease, 3 to MM and 1 to LPL. Neutropenia (76%) and anemia (70%) were the most common clinical presentation. None of the patients had rheumatoid arthritis. Treatment for the TLGL was variable with a number of different agents used listed in Table 1. 45% (n=10) of patients had an indolent course and did not receive specific therapy for TLGL. 6 patients responded to a single line of therapy, all of whom received either cyclophosphamide or methotrexate based regimens. The remainder had a relapsing course with multiple lines of therapy including 2 patients that received splenectomy. Nine patients were identified as having symptomatic multiple myeloma and TLGL, Table 2. Four patients had progressed from a preexisting plasma cell disorder, 3 with MGUS and 1 with SMM. The diagnosis of TLGL preceded myeloma in 1 patient was concurrent in 4 and post myeloma diagnosis in 4 patients. Time to diagnosis of TLGL post myeloma ranged from 10 to 63 months. At time of LGL diagnosis neutropenia was present in 7/9 patients and anemia in 6/8 (data unavailable for 1 patient). Cytogenetics data was available in 7 patients. Hyperdiploidy was the most common abnormality (3/7) followed by deletion 13q (2/7), t(14;16) in 1 patient and 1q amplification in 1 patient. The majority of patients were treated with novel agents with 7 receiving bortezomib based therapy. 3 patients underwent autologous stem cell transplantation. Therapy directed at the TLGL was given to 4/9 patients. This consisted of a combination of cyclophosphamide and prednisone in 3/4 patients all of whom responded to therapy with resolution of cytopenias. One patient had TLGL with multiple relapses and required multiple lines of therapy including eventual splenectomy. 3 patients with TLGL diagnosed after the diagnosis of myeloma did not receive specific therapy directed at the TLGL. The clinical course of the TLGL in these 3 patients was indolent and did not appear to be affected by therapy for multiple myeloma. At last follow up 5 patients have died. After a median follow up of 76 months post TLGL diagnosis the median overall survival (OS) post TLGL diagnosis was not reached for the entire cohort. In the cohort of patients with multiple myeloma, median OS from time of myeloma diagnosis was 71 months. Median OS from time of TLGL diagnosis was not reached. T-LGL leukemia can present in patients with a variety of plasma cell disorders and occur at any stage of the disease process. It is an important differential to consider in patients with unexplained cytopenias that are incongruent with the activity of the plasma cell disorder. Disclosures Dingli: Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding.


1998 ◽  
Vol 5 (3) ◽  
pp. 209-217 ◽  
Author(s):  
John A. Lust ◽  
Kathleen A. Donovan

Background Approximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma. Methods Studies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL- 6 and IL-1β, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed. Results IL-1β is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1β has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these “fixed” monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1β and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index. Conclusions A better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.


2020 ◽  
Vol 51 (4) ◽  
pp. 193-202
Author(s):  
Artur Jurczyszyn ◽  
Ruth Hutch ◽  
Anna Waszczuk-Gajda ◽  
Anna Suska ◽  
Katarzyna Krzanowska ◽  
...  

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder implicated as a precursor of multiple myeloma (MM), while smoldering multiple myeloma (SMM) is a malignant plasma cell disorder without evidence of a myeloma-defining event(s) (MDE). This is a review article of both disorders outlining their current definition and management according to the current standard of care. We focus on the pathogenesis of MM and the role of MGUS and SMM in the development of active MM. MGUS is a benign disorder and, subsequently, is followed by observation. In contrast, for SMM, although the current standard of care is “watch and wait”, this paper will explore the circumstances in which treatment should be considered to prevent MDE.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1828-1828 ◽  
Author(s):  
Steven Schuster ◽  
Angela Dispenzieri ◽  
S. Vincent Rajkumar ◽  
Alvaro Moreno Aspitia ◽  
Robert Kyle ◽  
...  

Abstract Abstract 1828 Poster Board I-854 Background IgM Multiple Myeloma (MM) and Waldenstrom's Macroglobulinemia (WM) are two hematologic diagnoses with the common variable of an IgM monoclonal gammopathy. Distinguishing these two diagnoses is critical as the approach to therapy is different. A study by Avet-Loiseau et al demonstrated the presence of t(11;14) translocations in 7 of 8 patients with IgM MM that was absent in all of a series of 17 cases of WM (Semin Oncol 2003 30:2;153). However, 6 of the 8 IgM MM cases lacked classic lytic lesions. Method A priori, based on the literature and the natural history of MM, we defined IgM MM as a symptomatic clonal plasma cell proliferative disorder characterized by a serum IgM monoclonal protein (regardless of size) plus presence of t(11;14) on fluorescent in situ hybridization (FISH) and/or lytic bone lesions felt to be related to the underlying plasma cell disorder. The cases for the study were screened by a computerized database search for ‘IgM’ and ‘Myeloma’ of all patients seen at Mayo Clinic in the last 30 years at all three sites (Rochester, Arizona and Florida). Patients identified on the computerized screen were then audited by chart review to identify the study cohort. Results 38 cases were identified on initial screen of the computerized database as potential patients with IgM MM. Of these, a total of 22 cases met our specific definition of IgM myeloma (t(11;14 and/or lytic lesions). Of the remaining 16 cases, 8 were IgM MGUS, 5 were WM based on clinical presentation (hyperviscosity, lymphadenopathy and organomegaly) and biopsy findings of lymphoplasmacytic lymphoma, 1 was excluded due to lack of information, and the remaining 2 patients were indeed considered to have clinical IgM MM. Interestingly, these two patients did not have either the t(11;14) or lytic lesions, but rather had immunophenotypic features suggestive of MM and not WM (CD138+, CD20-). Table 1 summarizes the clinical characteristics of the 22 patients who met our criteria for IgM MM. All 22 patients had lytic bone lesions. Of the 17 evaluated with FISH, 6 (35%) demonstrated the t(11;14) abnormality. Median overall survival by Kaplan-Meier analysis was 37 months represented in Figure 1. Conclusion IgM MM is a discrete clinical entity that can and should be distinguished from WM. Our definition of IgM MM is designed to be specific and requires the presence of a symptomatic IgM secreting plasma cell proliferative disorder plus presence of t(11;14) and/or lytic bone lesions felt related to the underlying plasma cell disorder. In this, the largest series of patients with IgM MM, the t(11;14) abnormality is very specific for IgM MM, but may not be sensitive, being present in approximately 1/3 of patients. The median overall survival is similar to non-IgM myeloma patients treated during this period, and much shorter than what would be expected for WM. The minority of symptomatic patients with IgM monoclonal gammopathy who do not meet this criteria, but have immunophenotypic features more suggestive of MM rather than WM need further study. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4869-4869
Author(s):  
Avni M Desai ◽  
Richard L Amdur ◽  
Min-Ling L Liu ◽  
Joao Ascensao ◽  
Dalia Mobarek ◽  
...  

Abstract Abstract 4869 The information regarding monoclonal gammopathy of unknown significance (MGUS) derives mainly from studies of Caucasian individuals. In contrast, this study describes the characteristics of 492 African American (AA) male patients identified with MGUS from the electronic database at the Washington VAMC. Review of their individual electronic records showed that none of the patients initially had evidence of myeloma or other symptomatic plasma cell or lymphoproliferative disorder. The median age at diagnosis of MGUS was 68 years old (range 28.5 to 95.6 years). The distribution of monoclonal immunoglobulin (M Ig) subtypes were IgG 78.1%, IgA 14.8%, IgM 6.9%; light chain only in the urine 2.9% or in the serum 1.0%, The light chain distribution of the M Igs was 60% kappa, 40% lambda. Fifty-nine patients (12%) had diclonal and 4 (0.8%) had triclonal M Igs. The median amount of M Ig was 0.26 g/dL; 47.8% were too small to quantitate. Ninety-four (25.5%) of 368 tested had Bence-Jones proteinuria, with a similar kappa:lambda distribution and 4 patients showed both light chains. Clinical characteristics were as follows: hepatitis C 15.5%, HIV 5.1%, other significant infections 26.8%, and chronic autoimmune or inflammatory disorders 10.3%. The patients were followed clinically for a median of 4.1 years (range 0.35 to 21.02 years), and the median interval between the first and last electrophoresis was 1.41 years (range 0 to 19.97 years). During this period 21 patients (4.3%) progressed to a malignant plasma cell disorder (myeloma 20, solitary plasmacytoma 1). 133 patients (27.0%) died of other causes, and in 26 (5.3%) the M protein had resolved. The actuarial risk determined by a Kaplan Meier plot of progression to a symptomatic plasma cell disorder was 13.5 % at 11 years. The initial M Ig in the patients who progressed was IgG in 15, IgA in 4, and isolated BJ proteinuria in 2. The only recognized predicting characteristic for progression was the detection of Bence-Jones proteinuria at diagnosis of MGUS: Thirteen of 20 (65%) progressing patients tested were positive as compared to 81 of 348 (23.0%) of the non-progressors (p = .0003) A number of features distinguish this AA MGUS cohort from previous series of Caucasian patients. MGUS was detected at an earlier age: 8.9% (5.2% excluding HCV and HIV patients) were under the age of 50. The percentage of AA patients with very low level M proteins was more than threefold that previously reported. The percentage of patients with IgM M Ig was less than one-half noted in previous studies. The actuarial risk of progression to a symptomatic plasma cell disorder as calculated from a Kaplan Meier plot appears to be comparable to previous reports in predominantly Caucasian series. Dr. Desai worked on this project following completion of her internal medicine residency. She is now a Hematology Oncology fellow at Montefiore Medical Center, New York NY. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Mert Erciyestepe ◽  
Tarık Onur Tiryaki ◽  
İpek Yönal Hindilerden ◽  
Gülçin Yeğen ◽  
Meliha Nalçacı

Multiple myeloma is a type of plasma cell disorder and can be seen in different forms. According to current knowledge, it is not a curable disease. Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma. We present a 53-year-old female patient who started with SMM which turned into multiple myeloma after four years. Despite 26 cycles of lenalidomide treatment, we performed the second autologous stem transplantation. After 12 years from the diagnosis of the disease, it was transformed into plasma cell leukemia and widespread nodular lesions were seen in the liver. Different presentations could be seen due to malignant plasma cell infiltrations or primary amyloidosis. Liver involvement is one of them and is less common than other organ involvement. We report a case of myeloma presenting with extensive nodular involvement in the liver and misdiagnosed as metastatic disease. It is important because of its rarity and change of the treatment approach.


2018 ◽  
Vol 12 (3) ◽  
pp. 737-746
Author(s):  
Toshiro Fukui ◽  
Yuji Tanimura ◽  
Yasushi Matsumoto ◽  
Shunsuke Horitani ◽  
Takashi Tomiyama ◽  
...  

Amyloid light-chain (AL) amyloidosis is associated with plasma cell disorder and monoclonal light chains. This type of amyloidosis is the prominent type involving the gastrointestinal tract. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and a known precursor of more serious diseases. A 72-year-old male was treated for high blood pressure, diabetes, and gout at the clinic of a private physician. Due to a positive fecal occult blood test discovered during colon cancer screening, he underwent colonoscopy and was diagnosed with adenomatous polyps by biopsies. Two months later, he was referred to our hospital for endoscopic resection of the polyps. Although the polyps were successfully removed, a colonoscopy revealed two types of ulcerative lesions. Immunohistopathological evaluations obtained from these lesions and polyps confirmed amyloid deposition. Although esophagogastroduodenoscopy results were normal, a biopsy specimen from the patient’s stomach showed the same type of amyloid deposition. Immunoelectrophoresis showed M-proteins for anti-IgG-λ in the serum and λ type Bence-Jones protein in the urine. His blood, bone marrow, and urine test results led to a diagnosis of MGUS. A coronary angiography revealed multivessel stenosis, and the patient’s cardiac function improved after coronary artery stenting. Hereafter, a combination therapy with bortezomib, lenalidomide, and dexamethasone is planned. This is a case report of systemic AL amyloidosis caused by MGUS, which was incidentally detected by colonoscopy.


2009 ◽  
Vol 2009 ◽  
pp. 1-2 ◽  
Author(s):  
Tommasina Guglielmelli ◽  
Roberta Merlini ◽  
Emilia Giugliano ◽  
Giuseppe Saglio

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least2×109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Zeinab A. Issa ◽  
Mira S. Zantout ◽  
Sami T. Azar

Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. It is characterized by accumulation of clonal plasma cells, predominantly in the bone marrow. The prevalence of type 2 diabetes is increasing; therefore, it is expected that there will be an increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is multifaceted. The coexistence of the two conditions in a patient forms a major challenge for physicians.


2020 ◽  
Vol 18 (12) ◽  
pp. 1720-1729
Author(s):  
Timothy M. Schmidt ◽  
Natalie S. Callander

The presence of monoclonal proteins is common, with a prevalence in the United States around 5% that increases with age. Although most patients are asymptomatic, most cases are caused by a clonal plasma cell disorder. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions with variable risk of progression to multiple myeloma. In recent years, significant progress has been made to better understand the factors that lead to the development of symptoms and progression to myeloma. This review summarizes the current diagnosis treatment guidelines for MGUS and SMM and highlights recent advances that underscore a shifting paradigm in the evaluation and management of plasma cell precursor conditions.


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