Asymptomatic Monoclonal Gammopathies

Bories, Claire; Jagannath, Sundar

doi:10.1016/j.clml.2014.05.004

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…This is in agreement with a previous study comparing gene expression in plasma cells from a MM patient with plasma cells from a genetically identical twin, in which up-regulation of FZR1 was identified [ 35 ]. MM is preceded by pre-malignant conditions, MGUS or smoldering myeloma, which progress to malignant MM at a rate of 1% and 10% per year, respectively [ 36 ]. Interrogation of dataset GSE6647 demonstrates that FZR1 expression is also upregulated in these precursor diseases, suggesting that dysregulation of FZR1 expression may occur early in the disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma

et al. 2016

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Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIα (TOPIIα) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIα levels were first increased through pre-treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM.

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Section: Discussionmentioning

confidence: 99%

Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma

et al. 2016

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“…8 Some of these cases ultimately lead to MM, which signifies the importance of further follow-up in specific circumstances. 9 Our patient underwent a bone marrow aspiration and biopsy in order to exclude the possibility of MM and remains still under regular supervision. As far as the therapeutic options are concerned, it has been observed that most patients with hemoglobin H disease rarely require blood transfusions.…”

Section: Discussionmentioning

confidence: 99%

Paraspinal extramedullary hematopoiesis in alpha-thalassemia with concurrent monoclonal gammopathy of undetermined significance: an uncommon case report

Tsifi¹,

Tsifis²,

Vieru³

et al. 2019

PPIJ

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Extramedullary hematopoiesis is a rare phenomenon, which consists of the formation of hematopoietic tissue in various parts of the human body due to the existence of a hematological disorder. Alpha-thalassemia is a great example of a disease that can result in extramedullary hematopoiesis. The present study reports an unusual case of a 64year-old male, who was diagnosed with hemoglobin H disease and secondary paraspinal extramedullary hematopoiesis with a concurrent monoclonal hypergammaglobulinemia. The lesion presented itself as a paraspinal mass of 4,5 cm extending longitudinally between the T9 and T10 vertebral bodies and it was accompanied by mild anemia and splenomegaly. The presence of monoclonal hypergammaglobulinemia and the fact that the patient was until recently a blood donor complicated our final diagnosis, which proved to be the coexistence of hemoglobin H disease and extramedullary hematopoiesis with monoclonal gammopathy of undetermined significance. This is the main reason why the diagnosis, differential diagnosis and treatment options of this rare case are discussed.

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“…A prior cohort study of a predominately white population in Olmsted County, Minnesota suggested that MGUS progresses to MM at a rate of approximately 1% per year with the 20-year cumulative risk totaling 18% 3 . However, due to the absence of population-based screening and treatment recommendations for MGUS 4 , 5 , most MGUS cases are detected incidentally 6 , and, thus, our understanding of MGUS and MM are primarily informed by clinical studies. Further work is needed to understand the natural history of MM and how it varies across age, gender, and race/ethnicity.…”

Section: Introductionmentioning

confidence: 99%

Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study

Huber,

Ji,

Shih

et al. 2023

Nat Commun

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Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.

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Asymptomatic Monoclonal Gammopathies

Cited by 8 publications

References 55 publications

Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma

Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma

Paraspinal extramedullary hematopoiesis in alpha-thalassemia with concurrent monoclonal gammopathy of undetermined significance: an uncommon case report

Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study

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