Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential

Paíno, Teresa; Paiva, Bruno; Jm, Sayagués; Mota, Inês; Carvalheiro, Tiago; La, Corchete; Aires-Mejía, Irene; Jj, Pérez; Sánchez, M-L; Bárcena, Paloma; Ocio, Enrique M.; San-Segundo, Laura; Sarasquete, María Eugenia; García‐Sanz, Ramón; Vidriales, María‐Belén; Oriol, Albert; Mt, Hernández; S.K., Edmond; Paiva, Artur; Bladé, Joan; Jj, Lahuerta; Órfão, Alberto; Mateos, M.V.; Nc, Gutiérrez; Miguel, Jesús F. San

doi:10.1038/leu.2014.321

Cited by 69 publications

(78 citation statements)

References 35 publications

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“…However, it is important to note that the baseline tumor clone often shows also phenotypic heterogeneity, and that all different phenotypic subclones should be followed throughout therapy (9). In fact, it has been recently shown that the distribution of such subclones may fluctuate from diagnostic into MRD samples, but this should be interpreted as clonal selection rather than antigenic shift upon therapy (9).…”

Section: Further Characterization Of Pcsmentioning

confidence: 99%

“…The power of this interpretation method is that it facilitates the development of a normal reference library of chosen cases, automated separation of populations within a sample taking into consideration all parameters, and prospective detection and tracking of any aberrant population that deviates from the normal cells. This can be particularly useful in cases with different subclones that can be difficult to identify when only bi-dimensional dot plots are used (9).…”

Section: The Role Of New/more Advanced Computational Tools To Facilitmentioning

confidence: 99%

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Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting

Arroz

Came

Lin

et al. 2015

Cytometry Part B Clinical

151

176

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Background: Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing.Methods: A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs ( 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM.Results/Conclusion: Consensus guidelines support i) the use of minimum of five initial gating parameters (CD38, CD138, CD45, forward, and sideward light scatter) within the same aliquot for accurate identification of the total plasma cell compartment; ii) the analysis of potentially aberrant phenotypic markers and to report the antigen expression pattern on neoplastic plasma cells as being reduced, normal or increased, when compared to a normal reference plasma cell immunophenotype (obtained using the same instrument and parameters); and iii) the percentage of total bone marrow plasma cells plus the percentages of both normal and neoplastic plasma cells within the total bone marrow plasma cell compartment, and over total bone marrow cells. Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 3 10 6 and 5 3 10 6 bone marrow cells to be measured, respectively. V C 2015 International Clinical Cytometry Society

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Section: Further Characterization Of Pcsmentioning

confidence: 99%

Section: The Role Of New/more Advanced Computational Tools To Facilitmentioning

confidence: 99%

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting

Arroz

Came

Lin

et al. 2015

Cytometry Part B Clinical

151

176

View full text Add to dashboard Cite

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“…It is important that a selected antigen is uniformly expressed on the malignancy targeted by CAR-T. 5,6,20,23 MM is a clonal malignancy, but over time, multiple subclones of MM evolve. [54][55][56][57][58] This leads to genetic and phenotypic heterogeneity of the MM cells within the same patient. 56,57,59 This phenotypic heterogeneity includes differences in cell-surface antigen expression.…”

Section: Rationale For Developing Car-t Therapies For MMmentioning

confidence: 99%

“…56,57,59 This phenotypic heterogeneity includes differences in cell-surface antigen expression. 58 As antigen expression can differ For personal use only. on May 12, 2018.…”

Section: Rationale For Developing Car-t Therapies For MMmentioning

confidence: 99%

Chimeric antigen receptor T-cell therapies for multiple myeloma

Mikkilineni¹,

Kochenderfer

2017

Blood

188

176

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Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM. Target antigens for CARs must be expressed on malignant cells, but expression on normal cells must be absent or limited. B-cell maturation antigen is expressed by normal and malignant plasma cells. CAR-Ts targeting B-cell maturation antigen have demonstrated significant antimyeloma activity in early clinical trials. Toxicities in these trials, including cytokine release syndrome, have been similar to toxicities observed in CAR-T trials for leukemia. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-Ts is a novel approach to MM therapy. MM antigens including CD138, CD38, signaling lymphocyte–activating molecule 7, and κ light chain are under investigation as CAR targets. MM is genetically and phenotypically heterogeneous, so targeting of >1 antigen might often be required for effective treatment of MM with CAR-Ts. Integration of CAR-Ts with other myeloma therapies is an important area of future research. CAR-T therapies for MM are at an early stage of development but have great promise to improve MM treatment.

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“…The revision will allow us to identify a range of specific genetic events in various B-cell and PC subsets, and to design research activities focused on targeted therapy, 99,100 based on prospectively sampled biomaterial from all myeloma subtypes classified at diagnosis and during follow-up. This strategy is in accordance with recent consensus statements on the definitions, assays, and nomenclature of CSCs, including a more operational nomenclature that achieves technical precision without completely abolishing established terminology.…”

Section: Summary and Perspectivementioning

confidence: 99%

The myeloma stem cell concept, revisited: from phenomenology to operational terms

et al. 2016

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Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential

Cited by 69 publications

References 35 publications

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting

Chimeric antigen receptor T-cell therapies for multiple myeloma

The myeloma stem cell concept, revisited: from phenomenology to operational terms

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