Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Paiva, Bruno; Corchete, Luis A.; Vidriales, María‐Belén; Puig, Noemí; Maiso, Patricia; Rodríguez, Idoia; Alignani, Diego; Burgos, Leire; Sánchez, Manuel González; Bárcena, Paloma; Echeveste, M Asuncion; Hernández, Miguel T.; García‐Sanz, Ramón; Ocio, Enrique M.; Oriol, Albert; Gironella, Mercedes; Palomera, Luis; Arriba, Felipe de; González, Yolanda; Johnson, Sarah K.; Epstein, Joshua; Barlogie, Bart; Lahuerta, Juan José; Bladé, Joan; Órfão, Alberto; Mateos, María‐Victoria; Miguel, Jesús F. San

doi:10.1182/blood-2015-08-665679

Cited by 83 publications

(75 citation statements)

References 58 publications

(64 reference statements)

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“…Paiva et al [15] provided very attractive data regarding the importance of the phenotypic and genetic characterization of these residual cells in order to understand chemoresistance. Our results show that a significant proportion of patients with CR/MRD+ can recover a subclonal pattern similar to MGUS.…”

Section: Discussionmentioning

confidence: 99%

Multiparameter Flow Cytometry Identification of Neoplastic Subclones: A New Biomarker in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

et al. 2018

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Multiparameter flow cytometry (MFC)-based clonality assessment is a powerful method of diagnosis and follow-up in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). However, the relevance of intraclonal heterogeneity in immunophenotypic studies remains poorly understood. The main objective of this work was to characterize the different immunophenotypic subclones in MGUS and MM patients and to investigate their correlation with disease stages. An 8-color MFC protocol with 17 markers was used to identify the subclones within the neoplastic compartment of 56 MGUS subjects, 151 newly diagnosed MM patients, 30 MM subjects in complete remission with detectable minimal residual disease, and 36 relapsed/refractory MM patients. Two or more clusters were observed in > 85% of MGUS subjects, 75% of stage I MM patients, and < 15% in stage III. Likewise, a significant correlation between the dominant subclone size, secondary cytogenetic features, and changes in the expression of CD27, CD44, and CD81 was detected. The loss of intraclonal equilibrium may be an important factor related with kinetics and risk of progression not well considered to date in MFC studies. The MFC strategy used in this work can provide useful biomarkers in MGUS and MM.

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Section: Discussionmentioning

confidence: 99%

Multiparameter Flow Cytometry Identification of Neoplastic Subclones: A New Biomarker in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

et al. 2018

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“…Putative drug resistant cells have shown gene expression to be both generally dysregulated and specifically altered involving, for instance, genes with a role in the cell’s processing of protein seen in relapsed proteasome inhibitor treated patients [28,55]. In addition, expression of multi-drug resistance ( MDR ) genes such as ATP binding cassette ( ABC ) genes can change after therapy [56].…”

Section: Risk Stratificationmentioning

confidence: 99%

“…Depth of response is related to OS [55]. New treatments have higher efficacy and therefore require more sensitive assessment of responses [71].…”

Section: Treatmentmentioning

confidence: 99%

“…There is a strong likelihood that MRD cells are drug resistant [55]. MRD cells may be “silent”, i.e., not secreting paraprotein and so impossible to detect via clinical biochemical means [55].…”

Section: Minimal Residual Disease (Mrd)mentioning

confidence: 99%

“…MRD cells may be “silent”, i.e., not secreting paraprotein and so impossible to detect via clinical biochemical means [55]. These cells may also have unique cytogenetic, genetic and immunophenotypic profiles [55].…”

Section: Minimal Residual Disease (Mrd)mentioning

confidence: 99%

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Towards Stratified Medicine in Plasma Cell Myeloma

Egan¹,

Drain²,

Conway³

et al. 2016

IJMS

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Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient’s age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as β-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.

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Persistent bone marrow minimal residual disease as a “high‐risk” disease feature in multiple myeloma

et al. 2021

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Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Cited by 83 publications

References 58 publications

Multiparameter Flow Cytometry Identification of Neoplastic Subclones: A New Biomarker in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Multiparameter Flow Cytometry Identification of Neoplastic Subclones: A New Biomarker in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Towards Stratified Medicine in Plasma Cell Myeloma

Persistent bone marrow minimal residual disease as a “high‐risk” disease feature in multiple myeloma

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