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Cancer stem cells of differentiated B-cell malignancies: models and consequences.

Gross E, Quillet-Mary A, Ysebaert L, Laurent G, Fournie JJ - Cancers (Basel) (2011)

Bottom Line: The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment.Proof of the principle is still lacking, however, in malignancies of differentiated B-cells.We propose two models accounting for cancer stem cells in these contexts: a "top-to-bottom" clonal hierarchy from memory B-cells and a "bottom-to-top" model of clonal reprogramming.

View Article: PubMed Central - PubMed

Affiliation: INSERM, UMR1037-Cancer Research Center of Toulouse, 31300 Toulouse, France. jean-jacques.fournie@inserm.fr.

ABSTRACT
The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a "top-to-bottom" clonal hierarchy from memory B-cells and a "bottom-to-top" model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

No MeSH data available.


Related in: MedlinePlus

Models of clonal progenies in normal and malignant contexts. Note that the difference between bottom-to-top models 1 and 2 is the target of the oncogenic hit.
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f2-cancers-03-01566: Models of clonal progenies in normal and malignant contexts. Note that the difference between bottom-to-top models 1 and 2 is the target of the oncogenic hit.

Mentions: We infer that cellular reprogramming can disrupt the initial clone pyramid and initiate the tumor in a reverse, “bottom-to-top” fashion. This does not necessarily refute the hierarchical paradigm of CSC, but rather requires a secondary, inducible “bottom-to-top” reprogramming of new clonal hierarchies. Although such “bottom-to-top” reprogramming has already been demonstrated for committed progenitors of AML and CML [52,53,60], evidence for the natural occurrence of molecular reprogramming in the pathogenesis of B-differentiated malignancy is still lacking. The fludarabine-induced switch of some non-SP cells into SP cells in B-CLL [43] may delineate such a “reprogramming” plasticity in malignant mature B cells. This induced reprogramming might not be restricted to responses to chemotherapeutic exposure [61,62] however, since different selective pressures usually edit oncogenesis and cancer progression. Oncogene insult [63,64] as well as hypoxia [65,66], microenvironmental signal [67,68] or cell migration [69,70] (e.g., epithelial-mesenchymal transition) might also induce “bottom-to-top” reprogramming. Since most diagnosed cancers have already been exposed to these pressures for growth, we hypothesize that reprogramming within the malignant clone is most likely to have occurred and yielded a heterogeneous and diversified cell progeny. However, classic (top-to-bottom) hierarchical reprogramming from the same upstream CSC is less prone to diversify this organization than the reverse (bottom-to-top) reprogramming from daughter cells (Figure 2).


Cancer stem cells of differentiated B-cell malignancies: models and consequences.

Gross E, Quillet-Mary A, Ysebaert L, Laurent G, Fournie JJ - Cancers (Basel) (2011)

Models of clonal progenies in normal and malignant contexts. Note that the difference between bottom-to-top models 1 and 2 is the target of the oncogenic hit.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757378&req=5

f2-cancers-03-01566: Models of clonal progenies in normal and malignant contexts. Note that the difference between bottom-to-top models 1 and 2 is the target of the oncogenic hit.
Mentions: We infer that cellular reprogramming can disrupt the initial clone pyramid and initiate the tumor in a reverse, “bottom-to-top” fashion. This does not necessarily refute the hierarchical paradigm of CSC, but rather requires a secondary, inducible “bottom-to-top” reprogramming of new clonal hierarchies. Although such “bottom-to-top” reprogramming has already been demonstrated for committed progenitors of AML and CML [52,53,60], evidence for the natural occurrence of molecular reprogramming in the pathogenesis of B-differentiated malignancy is still lacking. The fludarabine-induced switch of some non-SP cells into SP cells in B-CLL [43] may delineate such a “reprogramming” plasticity in malignant mature B cells. This induced reprogramming might not be restricted to responses to chemotherapeutic exposure [61,62] however, since different selective pressures usually edit oncogenesis and cancer progression. Oncogene insult [63,64] as well as hypoxia [65,66], microenvironmental signal [67,68] or cell migration [69,70] (e.g., epithelial-mesenchymal transition) might also induce “bottom-to-top” reprogramming. Since most diagnosed cancers have already been exposed to these pressures for growth, we hypothesize that reprogramming within the malignant clone is most likely to have occurred and yielded a heterogeneous and diversified cell progeny. However, classic (top-to-bottom) hierarchical reprogramming from the same upstream CSC is less prone to diversify this organization than the reverse (bottom-to-top) reprogramming from daughter cells (Figure 2).

Bottom Line: The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment.Proof of the principle is still lacking, however, in malignancies of differentiated B-cells.We propose two models accounting for cancer stem cells in these contexts: a "top-to-bottom" clonal hierarchy from memory B-cells and a "bottom-to-top" model of clonal reprogramming.

View Article: PubMed Central - PubMed

Affiliation: INSERM, UMR1037-Cancer Research Center of Toulouse, 31300 Toulouse, France. jean-jacques.fournie@inserm.fr.

ABSTRACT
The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a "top-to-bottom" clonal hierarchy from memory B-cells and a "bottom-to-top" model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

No MeSH data available.


Related in: MedlinePlus