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The cancer stem cell model: B cell acute lymphoblastic leukaemia breaks the mould.

McClellan JS, Majeti R - EMBO Mol Med (2012)

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Hematology, Institute for Stem Cell Biology and Regenerative Medicine, and Cancer Institute, Stanford University School of Medicine, Palo Alto, CA, USA.

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See related article in EMBO Molecular Medicine http://dx.doi.org/10.1002/emmm.201201703 The cancer stem cell (CSC) hypothesis postulates that tumours are arranged in a developmental hierarchy reflecting heterogeneity on the cellular level... Subsequent work has demonstrated that CSCs in most cases of AML comprise a subpopulation of cells that express several cell surface markers in common with normal hematopoietic stem and progenitor cells, as well as other leukaemia stem cell (LSC)-specific surface markers (Majeti, )... They report that LSC are not enriched in blast populations expressing either CD34 or CD10, both markers of immaturity in the hierarchy of normal B cell development... This is true of the markers CD10 and CD20 as well. »…the findings of Rehe et al suggest that B-ALL cells are not arranged in a strict hierarchy…« Impressively, the authors further utilize limiting dilution xenotransplantation assays to calculate the LSC frequency in the B-ALL samples, and subpopulations isolated based on differential expression of CD10, CD20 or CD34... Taken together, the findings of Rehe et al suggest that B-ALL cells are not arranged in a strict hierarchy, and that LSC activity is frequent and cannot be isolated by immunophenotypic markers of normal B cell differentiation... More recently, AML LSC were shown to have a gene expression profile distinct from the bulk of the leukemic blasts (Eppert et al, ; Gentles et al, )... Not surprisingly, genes associated with self-renewal were preferentially expressed in AML LSC... With this in mind, Rehe et al examined the transcriptional profile of CD34 B-ALL blasts and phenotypically more mature CD34 B-ALL blasts... Consistent with their xenograft data, they found no distinction between these two populations with regard to their expression of candidate stem cell genes... Additionally, unlike previous studies, Rehe et al transferred cell suspensions directly into the bone marrow cavity using intrafemoral injection, a technique that likely allowed these cells better access to a favourable niche... Taken together, the authors' findings suggest that the hierarchical LSC model of AML does not apply to B-ALL (Fig 1)... The authors propose the various immunophenotypically defined subpopulations seen in B-ALL do not differ in a biologically meaningful way, but rather represent stochastic differences in gene expression... Does the plasticity in immunophenotype reflect an underlying plasticity of B-ALL blasts? Most fundamentally, why does AML maintain a hierarchy similar to normal hematopoiesis while B-ALL does not appear to follow such a paradigm?

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Contrasting cancer stem cell modelsAML follows a hierarchical model in which more mature blasts lose stem cell capacity.B-ALL may follow a stochastic model by which most, if not all, cells within the tumor are able to transplant the disease in xenograft models, and there is no strict hierarchy.
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fig01: Contrasting cancer stem cell modelsAML follows a hierarchical model in which more mature blasts lose stem cell capacity.B-ALL may follow a stochastic model by which most, if not all, cells within the tumor are able to transplant the disease in xenograft models, and there is no strict hierarchy.

Mentions: Taken together, the authors' findings suggest that the hierarchical LSC model of AML does not apply to B-ALL (Fig 1). The authors propose the various immunophenotypically defined subpopulations seen in B-ALL do not differ in a biologically meaningful way, but rather represent stochastic differences in gene expression. They further propose that most, if not all, B-ALL blasts are capable of recapitulating a tumour under the right circumstances. The clinical relevance of these findings is unclear, but they do suggest that therapies designed to target only a subset of B-ALL blasts will not be successful at curing patients.


The cancer stem cell model: B cell acute lymphoblastic leukaemia breaks the mould.

McClellan JS, Majeti R - EMBO Mol Med (2012)

Contrasting cancer stem cell modelsAML follows a hierarchical model in which more mature blasts lose stem cell capacity.B-ALL may follow a stochastic model by which most, if not all, cells within the tumor are able to transplant the disease in xenograft models, and there is no strict hierarchy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569649&req=5

fig01: Contrasting cancer stem cell modelsAML follows a hierarchical model in which more mature blasts lose stem cell capacity.B-ALL may follow a stochastic model by which most, if not all, cells within the tumor are able to transplant the disease in xenograft models, and there is no strict hierarchy.
Mentions: Taken together, the authors' findings suggest that the hierarchical LSC model of AML does not apply to B-ALL (Fig 1). The authors propose the various immunophenotypically defined subpopulations seen in B-ALL do not differ in a biologically meaningful way, but rather represent stochastic differences in gene expression. They further propose that most, if not all, B-ALL blasts are capable of recapitulating a tumour under the right circumstances. The clinical relevance of these findings is unclear, but they do suggest that therapies designed to target only a subset of B-ALL blasts will not be successful at curing patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Hematology, Institute for Stem Cell Biology and Regenerative Medicine, and Cancer Institute, Stanford University School of Medicine, Palo Alto, CA, USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

See related article in EMBO Molecular Medicine http://dx.doi.org/10.1002/emmm.201201703 The cancer stem cell (CSC) hypothesis postulates that tumours are arranged in a developmental hierarchy reflecting heterogeneity on the cellular level... Subsequent work has demonstrated that CSCs in most cases of AML comprise a subpopulation of cells that express several cell surface markers in common with normal hematopoietic stem and progenitor cells, as well as other leukaemia stem cell (LSC)-specific surface markers (Majeti, )... They report that LSC are not enriched in blast populations expressing either CD34 or CD10, both markers of immaturity in the hierarchy of normal B cell development... This is true of the markers CD10 and CD20 as well. »…the findings of Rehe et al suggest that B-ALL cells are not arranged in a strict hierarchy…« Impressively, the authors further utilize limiting dilution xenotransplantation assays to calculate the LSC frequency in the B-ALL samples, and subpopulations isolated based on differential expression of CD10, CD20 or CD34... Taken together, the findings of Rehe et al suggest that B-ALL cells are not arranged in a strict hierarchy, and that LSC activity is frequent and cannot be isolated by immunophenotypic markers of normal B cell differentiation... More recently, AML LSC were shown to have a gene expression profile distinct from the bulk of the leukemic blasts (Eppert et al, ; Gentles et al, )... Not surprisingly, genes associated with self-renewal were preferentially expressed in AML LSC... With this in mind, Rehe et al examined the transcriptional profile of CD34 B-ALL blasts and phenotypically more mature CD34 B-ALL blasts... Consistent with their xenograft data, they found no distinction between these two populations with regard to their expression of candidate stem cell genes... Additionally, unlike previous studies, Rehe et al transferred cell suspensions directly into the bone marrow cavity using intrafemoral injection, a technique that likely allowed these cells better access to a favourable niche... Taken together, the authors' findings suggest that the hierarchical LSC model of AML does not apply to B-ALL (Fig 1)... The authors propose the various immunophenotypically defined subpopulations seen in B-ALL do not differ in a biologically meaningful way, but rather represent stochastic differences in gene expression... Does the plasticity in immunophenotype reflect an underlying plasticity of B-ALL blasts? Most fundamentally, why does AML maintain a hierarchy similar to normal hematopoiesis while B-ALL does not appear to follow such a paradigm?

Show MeSH
Related in: MedlinePlus