Demystifying Biclonal Gammopathy: A Pathologist’s Perspective

Sharma, Sudha; Gupta, Parikshaa; Aggarwal, Ritu; Malhotra, Pankaj; Minz, Ranjana Walker; Bansal, Frainey

doi:10.1093/labmed/lmz006

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…On a similar line, Corradini et al identified pre‐CSR B‐cells carrying the same IGH clonotypic rearrangement of myeloma cells but expressing μ chains 24 . The presence of a pre‐CSR MM precursor would also provide the biological basis for the rare condition of bi‐clonal gammopathies, which have been described in several reports 24–26 . Other groups have described memory B‐cells recirculating through lymph nodes and peripheral blood with homing/spreading capacity through the BM carrying the MM‐specific clonotypic rearrangement 27,28 .…”

Section: From the Cell Of Origin To Pre‐malignant Stagesmentioning

confidence: 87%

“…24 The presence of a pre-CSR MM precursor would also provide the biological basis for the rare condition of bi-clonal gammopathies, which have been described in several reports. [24][25][26] Other groups have described memory B-cells recirculating through lymph nodes and peripheral blood with homing/spreading capacity through the BM carrying the MM-specific clonotypic rearrangement. 27,28 Besides confirming a GC origin of MM, these studies highlighted the possibility that the aberrant plasma cell clone in MM is repopulated from phenotypically distinct "stem" cells.…”

Section: Introductionmentioning

confidence: 99%

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A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

et al. 2020

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The knowledge of cancer origin and the subsequent tracking of disease evolution represent unmet needs that will soon be within clinical reach. This will provide the opportunity to improve patient's stratification and to personalize treatments based on cancer biology along its life history. In this review, we focus on the molecular pathogenesis of multiple myeloma (MM), a hematologic malignancy with a well-known multi-stage disease course, where such approach can sooner translate into a clinical benefit. We describe novel insights into modes and timing of disease initiation. We dissect the biology of the preclinical and pre-malignant phases, elucidating how knowledge of the genomics of the disease and the composition of the microenvironment allow stratification of patients based on risk of disease progression. Then, we explore cell-intrinsic and cell-extrinsic drivers of MM evolution to symptomatic disease. Finally, we discuss how this may relate to the development of refractory disease after treatment. By integrating an evolutionary view of myeloma biology with the recent acquisitions on its clonal heterogeneity, we envision a way to drive the clinical management of the disease based on its detailed biological features more than surrogates of disease burden.

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Section: From the Cell Of Origin To Pre‐malignant Stagesmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

et al. 2020

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“…Patients with double monoclonal gammopathic manifestations (DMGMs) can express two different M proteins that differ based on the presence of heavy chain (HC) isotypes with the same light chains (LCs) or LC isotypes with the same HC isotype (16). Our patient exhibited DMGMs (IgA κ and IgG κ).…”

Section: Discussionmentioning

confidence: 92%

Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen

Yan

Zhou

et al. 2021

Front. Med.

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Primary tracheobronchial light chain (AL) amyloidosis is a rare and heterogeneous disease characterized by the buildup of amyloid deposits in the airway mucosa. Although its treatment remains challenging, the current view is that the localized form can be treated conservatively due to its slow progression. While radiotherapy has proven effective in treating localized form of the disease, some patients do not respond to local treatment and continue to experience poor quality of life, highlighting the need to explore additional treatment strategies. In this report, we discuss a case of primary tracheobronchial AL amyloidosis with biclonal gammopathy (IgA κ and IgG κ) in a 46-year-old man who was transferred to our hospital due to dyspnea progression over the preceding 3 years. Chest computed tomography revealed irregular tracheobronchial stenosis with wall thickening, and histological examination of the bronchial biopsies confirmed the diagnosis of endobronchial AL amyloidosis. Owing to the poor effect of radiation therapy and treatments for improving airway patency, he was treated with a systemic chemotherapy regimen [cyclophosphamide-bortezomib-dexamethasone (CyBorD)]. We observed substantial improvements in his dyspnea, highlighting the potential of systemic therapy to improve quality of life of patients with tracheobronchial AL amyloidosis. However, the long-term pathological changes associated with local bronchial lesions require further investigation.

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“…Sharma et al reported a rate of 1.6% (15/916). [ 8 ] Meanwhile, Kyle et al reported a rate of 1.5% (57/3447), [ 9 ] but since they did not include the BG patients with Bence Jones proteinemia, the actual rate may be higher. The frequency reported by Guastafierro et al was 4% (49/1214), [ 10 ] but they excluded cases of double IgA-κ and double IgA-λ, citing the possibility of false positives due to IgA glycosylation and its tendency to polymerize.…”

Section: Discussionmentioning

confidence: 99%

Involvement of activation induced cytidine deaminase in malignant B-cells expressing two distinct M-components as an etiology of biclonal gammopathy

et al. 2022

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Biclonal gammopathy (BG) is a rare phenomenon in which 2 M proteins are detected in the same patient, with 2 major hypotheses regarding its etiology. One potential explanation is that completely different malignant B-cell clones produce different M proteins, while the other is that there is a malignant clone that produces both M proteins simultaneously. In this study, we examined 2 cases of B-cell malignancy with BG and found that some cells were double positive for both M proteins by immunofluorescence and flow cytometry. However, most of the remaining cells were single positive cells that produced only one of the M proteins. We hypothesized that double positive cells were in the process of transitioning from 1 single positive cell to another single positive cell, and that class switch recombination (CSR) would be involved as a mechanism. We then examined the expression of activation induced cytidine deaminase (AICDA), which is responsible for CSR, and found that lymphoma/myeloma cells in 2 BG patients were positive for AICDA by immunostaining. Our study is the first report suggesting that AICDA may be involved in the pathogenesis of BG.

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Demystifying Biclonal Gammopathy: A Pathologist’s Perspective

Cited by 10 publications

References 10 publications

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen

Involvement of activation induced cytidine deaminase in malignant B-cells expressing two distinct M-components as an etiology of biclonal gammopathy

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