Immunophenotypic studies of monoclonal gammopathy of undetermined significance

Horatiu Olteanu, Huan You Wang, Weina Chen, Robert W. McKenna, Nitin J. Karandikar

Research output: Contribution to journalArticle

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Abstract

Background. Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM. Methods. Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains. Results. All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32%, mean 3.3%, p ≪ 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p ≪ 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p ≪ 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p ≪ 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM. Conclusion. MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.

Original languageEnglish (US)
Article number13
JournalBMC Clinical Pathology
Volume8
Issue number1
DOIs
StatePublished - 2008

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Monoclonal Gammopathy of Undetermined Significance
Plasma Cells
Multiple Myeloma
Disease Progression
B-Cell Antigen Receptors
Paraproteinemias
Fluorescence
Immunoglobulin Light Chains
Phenotype
Cluster Analysis
Flow Cytometry
Color
Bone Marrow

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Immunophenotypic studies of monoclonal gammopathy of undetermined significance. / Olteanu, Horatiu; Wang, Huan You; Chen, Weina; McKenna, Robert W.; Karandikar, Nitin J.

In: BMC Clinical Pathology, Vol. 8, No. 1, 13, 2008.

Research output: Contribution to journalArticle

Olteanu, Horatiu ; Wang, Huan You ; Chen, Weina ; McKenna, Robert W. ; Karandikar, Nitin J. / Immunophenotypic studies of monoclonal gammopathy of undetermined significance. In: BMC Clinical Pathology. 2008 ; Vol. 8, No. 1.
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abstract = "Background. Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25{\%} of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM. Methods. Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains. Results. All MGUS patients had two subpopulations of plasma cells, one with a {"}normal{"} phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86{\%} (mean 27{\%}) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32{\%}, mean 3.3{\%}, p ≪ 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1{\%}) vs. 13/29 (45{\%}), p ≪ 0.001] and more likely to express surface immunoglobulin [21/32 (66{\%}) vs. 3/28 (11{\%}), p ≪ 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p ≪ 0.001]. There were no significant differences in CD56 expression [23/32 (72{\%}) vs. 18/29 (62{\%}), p = 0.29], CD45 expression [15/32 (47{\%}) vs. 20/30 (67{\%}), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33{\%}) with >90{\%} CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10{\%} CD19(+) plasma cells evolved to PCM. Conclusion. MGUS cases with potential for disease progression appeared to lack CD19 expression on >90{\%} of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.",
author = "Horatiu Olteanu and Wang, {Huan You} and Weina Chen and McKenna, {Robert W.} and Karandikar, {Nitin J.}",
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AU - Wang, Huan You

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AU - McKenna, Robert W.

AU - Karandikar, Nitin J.

PY - 2008

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N2 - Background. Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM. Methods. Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains. Results. All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32%, mean 3.3%, p ≪ 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p ≪ 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p ≪ 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p ≪ 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM. Conclusion. MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.

AB - Background. Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM. Methods. Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains. Results. All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32%, mean 3.3%, p ≪ 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p ≪ 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p ≪ 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p ≪ 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM. Conclusion. MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.

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