“Benign” Monoclonal Gammopathy—After 20 to 35 Years of Follow-Up

Kyle, Robert A.

doi:10.1016/s0025-6196(12)60015-9

Cited by 289 publications

(157 citation statements)

References 19 publications

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“…12 MGUS is found in approximately 1% of those older than 50 years and 3% of those over 70 years. Kyle has followed a group of 241 patients with MGUS for 20 to 35 years, [12][13][14][15] and categorized their clinical course: 19% had no significant change, 10% had an increase in monoclonal gammopathy to over 3.0 g/dl without an associated disorder, 47% died of unrelated disease and 24% went on to develop a plasma cell disorder. Of these patients, 66% developed multiple myeloma, 12% macroglobinemia, 14% amyloidosis and 8% other lymphoproliferative disease after a median follow-up of 10 years from the recognition of the gammopathy.…”

Section: Monoclonal Gammopathy and The Progression To Myelomamentioning

confidence: 99%

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Fiorino

Atac

1997

Leukemia

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We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.

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Section: Monoclonal Gammopathy and The Progression To Myelomamentioning

confidence: 99%

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Fiorino

Atac

1997

Leukemia

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“…Follow-up studies revealed that a large fraction of patients with MG evolve into myeloma or another lymphoplasmacytic disorder. The actuarial probability of malignant transformation is estimated to be around 5-10, 15-20, 25-35, and 30 -40% at 5, 10 and 20, and 25 years (11)(12)(13)(14)(15)(16)(17). There is no a reliable single variable to predict this transformation.…”

Section: Introductionmentioning

confidence: 99%

Immunophenotypic Aberrations, DNA Content, and Cell Cycle Analysis of Plasma Cells in Patients with Myeloma and Monoclonal Gammopathies

Lima

Teixeira

Fonseca

et al. 2000

Blood Cells, Molecules, and Diseases

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ABSTRACT:We describe the immunophenotypic and gross DNA defects in 55 patients with myeloma and 50 patients with monoclonal gammopathy and review the literature on this subject (MedLine, 1994(MedLine, -2000. Our data confirmed previous reports indicating that in myeloma nearly all marrow plasma cells are abnormal (98.7 Ϯ 8.1%). In monoclonal gammopathy the fraction of abnormal plasma cells was 35.0 Ϯ 32.8%. In both myeloma and monoclonal gammopathy, the most frequent aberrant phenotypic features consisted of absence of expression of CD19, strong expression of CD56, and decreased intensity of expression of CD38; aberrant expression of CD10, CD20, CD22, or CD28 was observed in less than one-third of myeloma cases. The vast majority of cases had two or more phenotypic aberrations. In the DNA studies, 7% of myeloma cases were biclonal and 93% of cases were monoclonal. In those studies with only one plasma cell mitotic cycle, 37% had normal DNA content and 63% were aneuploid (hyperploid, 61%; hypoploid, 2%). The mean percentages of plasma cells in S-and G2M phases were 4.9 Ϯ 8.5 and 4.4 Ϯ 6.9%, respectively. Thirty-eight percent of cases had more than 3% of plasma cells in S phase. In monoclonal gammopathy, the DNA index of abnormal plasma cells ranged from 0.89 to 1.30 and the percentage of diploid (31%) and aneuploid (69%) cases was not different from the results found in myeloma. The differences in percentage of abnormal plasma cells in S-(7.4 Ϯ 8.6%) and G2M-phases (2.4 Ϯ 1.7%) in patients with monoclonal gammopathy were not statistically significant.

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“…2 In a follow-up of 241 patients with MGUS, 59 patients (24.5%) went on to develop MM or a related plasma cell disorder. 3 Closer examination of those individuals who developed MM revealed that the majority of patients remained stable for an extended duration and then subsequently progressed to overt MM over a relatively short period of time. Of the 59 patients that progressed, 39 went on to develop multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

“…Seven of these 25 progressed rapidly in less than 1 year after a stable period of 2-25 years (median 8). 3 Based on these clinical observations, we hypothesized that MGUS and MM are biologically distinct entities and that one or more genetic changes occur in MGUS cells that are responsible for the progression of MGUS to MM.…”

Section: Introductionmentioning

confidence: 99%

Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma

et al. 1998

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We investigated whether differences in IL-6 and IL-1␤ expression could be detected in monoclonal plasma cells from patients with MGUS or MM. Expression of IL-6 and IL-1␤ in bone marrow cells was determined using cell sorting to enrich for plasma cells followed by reverse transcriptase/polymerase chain reaction (RT/PCR). Nineteen patients (six MGUS, two primary amyloid (AL), 11 MM) were studied. IL-6 mRNA expression was detectable in the sorted CD38 ؉ /CD45 ؊ plasma cell populations from 0/6 MGUS, 0/2 AL and 5/11 MM patients. All five MM patients with autocrine IL-6 expression demonstrated an elevated plasma cell labeling index. IL-1␤ mRNA was detectable in the sorted CD38 ؉ /CD45 ؊ plasma cell populations from 1/6 MGUS, 0/2 AL and 10/11 MM patients. In situ hybridization (ISH) confirmed that the IL-1␤ producing cells were plasma cells. In conclusion, autocrine production of IL-6 parallels a high labeling index and aberrant expression of IL-1␤ correlates with the diagnosis of MM. Follow-up of IL-1␤-positive MGUS patients will determine whether aberrant expression of IL-1␤ will predict those MGUS patients that will eventually progress to MM.

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“Benign” Monoclonal Gammopathy—After 20 to 35 Years of Follow-Up

Cited by 289 publications

References 19 publications

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Immunophenotypic Aberrations, DNA Content, and Cell Cycle Analysis of Plasma Cells in Patients with Myeloma and Monoclonal Gammopathies

Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma

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