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

Johnsen, Hans Erik; Bøgsted, Martin; Schmitz, Alexander; Bødker, Julie Støve; El‐Galaly, Tarec Christoffer; Johansen, Preben; Valent, Peter; Zojer, Niklas; Valckenborgh, Els Van; Vanderkerken, Karin; Duin, Mark van; Sonneveld, Pieter; Pérez-Andrés, Martín; Órfão, Alberto; Dybkær, Karen

doi:10.3324/haematol.2015.138826

Cited by 57 publications

(45 citation statements)

References 96 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such bone marrow cells have also been detected in various haematological malignancies [467]; in these cases, this monocyte subset seems to support the growth of malignant cells [467]. Bone marrow monocytes may, thereby, support the survival and growth of myeloma stem cells [468]. Our study should, therefore, be regarded as population-based and including unselected patients; for this reason, it is likely that our patients constitute a representative cohort.…”

Section: Discussionmentioning

confidence: 82%

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Rundgren

Bruserud

Ryningen

et al. 2018

Journal of Immunological Methods

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 82%

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Rundgren

Bruserud

Ryningen

et al. 2018

Journal of Immunological Methods

View full text Add to dashboard Cite

show abstract

“…Various experimental arguments support the first model ( 77 ), especially the fact that B-cell populations related to the malignant PC clone are not universally detected ( 78 ), while other works suggest that origins of MGUS and MM reside in the germinal center B-cells ( 79 ). Indeed, recent results showed that a rare subpopulation of early oncogene-positive memory-like B cells in lymph node, blood, and bone marrow is descended from the cell of origin in the germinal center ( 80 ). These cells would differentiate into premalignant PC in the bone marrow, propagate through peripheral blood, and give rise to a benign neoplasia, clinically known as MGUS.…”

Section: A New Model In Which Tissue Disruption Is the Initiator Evenmentioning

confidence: 99%

Multiple Myeloma Exemplifies a Model of Cancer Based on Tissue Disruption as the Initiator Event

Capp

Bataille

2018

Front. Oncol.

View full text Add to dashboard Cite

The standard model of multiple myeloma (MM) oncogenesis is based on the genetic instability of MM cells and presents its evolution as the emergence of clones with more and more aggressive genotypes, giving them surviving and proliferating advantage. The micro-environment has a passive role. In contrast, many works have shown that the progression of MM is also characterized by the selection of clones with extended phenotypes able to destroy bone trabeculae, suggesting a major role for early micro-environmental disruption. We present a model of MM oncogenesis in which genetic instability is the consequence of the disruption of normal interactions between plasma cells and their environment, the bone remodeling compartment. These interactions, which normally ensure the stability of the genotypes and phenotypes of normal plasma cells could be disrupted by many factors as soon as the early steps of the disease (MGUS, pre-MGUS states). Therapeutical implications of the model are presented.

show abstract

“…This limitation is broadly recognized and represents a considerable challenge, technically and bioinformatically. Understanding the genetic diversity and how it changes in response to interventions, will require deep sequencing and analysis of the genomes of highly selected single cells [47, 48]. …”

Section: Discussionmentioning

confidence: 99%

Molecular classification of tissue from a transformed non-Hogkin’s lymphoma case with unexpected long-time remission

et al. 2017

View full text Add to dashboard Cite

BackgroundThe concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www.hemaclass.org. We expected that such a study could generate therapeutic information and a frame for future individual evaluation of molecular resistance detected at clinical relapse.Case presentationThe patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III and treated with conventional R-CHOP [rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (P)]. Unfortunately, she suffered from severe toxicity but recovered during the following 6 months’ remission until biopsy-verified relapse. The patient refused second-line combination chemotherapy, but accepted 3 months’ palliation with R and chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present >9 years after primary diagnosis. Molecular studies and data evaluation by principal component analysis, mutation screening and copy number variations of the primary and relapsed tumor, identified a pattern of branched lymphoma evolution, most likely diverging from an in situ follicular lymphoma. Accordingly, the primary diagnosed transformed lymphoma was classified as a diffuse large B cell lymphoma (DLBCL) of the GCB/centrocytic subtype by “cell of origin BAGS” assignment and R sensitive and C, H, O and P resistant by “drug specific REGS” assignment. The relapsed DLBCL was classified as NC/memory subtype and R, C, H sensitive but O and P resistant.ConclusionsThorough analysis of the tumor DNA and RNA documented a branched evolution of the two clinical diagnosed tFL, most likely transformed from an unknown in situ lymphoma. Classification of the malignant tissue for drug-specific resistance did not explain the unexpected long-term remission and potential cure. However, it is tempting to consider the anti-CD20 immunotherapy as the curative intervention in the two independent tumors of this case.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-016-0063-0) contains supplementary material, which is available to authorized users.

show abstract

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

Cited by 57 publications

References 96 publications

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Multiple Myeloma Exemplifies a Model of Cancer Based on Tissue Disruption as the Initiator Event

Molecular classification of tissue from a transformed non-Hogkin’s lymphoma case with unexpected long-time remission

Contact Info

Product

Resources

About