Identification of hematopoietic stem/progenitor cells: strength and drawbacks of functional assays

Coulombel, Laure

doi:10.1038/sj.onc.1207941

Cited by 99 publications

(76 citation statements)

References 169 publications

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“…In the presence of dacinostat or vorinostat, colony formation of AML1/ ETO-positive cells was significantly reduced from the third plating on and completely abrogated at the sixth plating. Using PLZF/RARα-positive cells, the same results were obtained for spleen colony-forming unit (CFU-S) assays 20 by transplanting all progeny grown from 2.5 × 10 4 mock or LAFP-transduced Sca1 + / lin -cells, i.e., 15-30 × 10 4 untreated and 1-6 × 10 4 DACi-treated cells. Spleen colony formation was not affected by exposure to DACi in mice receiving mock-transduced cells (Fig.…”

Section: Resultssupporting

confidence: 50%

“…30 Serial replating and day 12 spleen colony-forming unit assays (CFU-S) are thus both suitable to detect functional, selfrenewing LSC. 20 We observed a dose-dependent suppression of the self-renewal capacity of AML1/ETO-positive cells by dacinostat and vorinostat. This observation is consistent with a gradual loss of self-renewing LSC over time and is in agreement with our previous report demonstrating a diminishing replating capacity of PLZF/RARα-positive LSC upon dacinostat treatment.…”

Section: Discussionmentioning

confidence: 78%

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Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells

et al. 2012

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Section: Resultssupporting

confidence: 50%

Section: Discussionmentioning

confidence: 78%

Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells

et al. 2012

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“…24 As shown in Figure 4a (Figures 4b and c). The numbers of both DEK/CAN-and PML/RARa-positive cells in the ST re-population were higher than in controls, and the DEK/CAN-mediated effect was statistically significant (Figure 4c).…”

Section: Dek/can Increases the St-hsc Potential But Not The Long-termentioning

confidence: 69%

“…Considering that CFU-S12 mainly detects early progenitors and cells with ST-HSC potential, 24 the fact that cells derived from the colonies from mock-infected ST-HSCs took root and produced a higher number of spleen colonies than mock-infected LT-HSCs represents a good control for the functional integrity of the cells. Nearly no difference was seen between the DEK/CAN-positive LT-HSCs and ST-HSCs in terms of their capacity to induce spleen colonies (Supplementary Figures 3b and c).…”

Section: Dek/can Induces Leukemia From Thementioning

confidence: 99%

The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation

et al. 2010

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The t(6;9)-positive acute myeloid leukemia (AML) is classified as a separate clinical entity because of its early onset and poor prognosis. The hallmark of t(6;9) AML is the expression of the DEK/CAN fusion protein. The leukemogenic potential of DEK/ CAN has been called into question, because it was shown to be unable to block the differentiation of hematopoietic progenitors. We found that DEK/CAN initiated leukemia from a small subpopulation within the hematopoietic stem cell (HSC) population expressing a surface marker pattern of long-term (LT) HSC. The propagation of established DEK/CAN-positive leukemia was not restricted to the LT-HSC population, but occurred even from more mature and heterogeneous cell populations. This finding indicates that in DEK/CAN-induced leukemia, there is a difference between 'leukemia-initiating cells' (L-ICs) and 'leukemia-maintaining cells' (L-MCs). In contrast to the L-IC cells represented by a very rare subpopulation of LT-HSC, the L-MC seem to be represented by a larger and phenotypically heterogeneous cell population.

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“…In the late 1970's, colony-forming soft agar assays emerged as a means by which scientists attempted to study the nature and potential of human tumor stem cells. 36,37 These in vitro colony-forming assays have facilitated insight into the differentiation potential and relationship of hematopoietic stem and progenitor cell populations in normal hematopoiesis and hematopoietic malignancies; 38 however, little practical insight has been garnered in solid tissues and tumors. Traditional cell lines originally derived from patient tumors and adapted to proliferate in in vitro culture conditions have been widely established and studied for more than a half century.…”

Section: Traditional Models Have Not Predicted Clinical Successmentioning

confidence: 99%

Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

Williams

Anderson

Santaguida

et al. 2013

Laboratory Investigation

165

166

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Cancer is a heterogeneous disease manifest in many forms. Tumor histopathology can differ significantly among patients and cellular heterogeneity within tumors is common. A primary goal of cancer biologists is to better understand tumorigenesis and cancer progression; however, the complex nature of tumors has posed a substantial challenge to unlocking cancer's secrets. The cancer stem cell (CSC) paradigm for the pathobiology of solid tumors appropriately acknowledges phenotypic and functional tumor cell heterogeneity observed in solid tumors and accounts for the disconnect between drug approval based on response and the general inability of approved therapies to meaningfully impact survival due to their failure to eradicate these most important of cellular targets. First proposed to exist decades ago, CSC have only recently begun to be precisely identified due to technical advancements that facilitate identification, isolation, and interrogation of distinct tumor cell subpopulations with differing ability to form and perpetuate tumors. Precise identification of CSC populations and the complete hierarchy of cells within solid tumors will facilitate more accurate characterization of patient subtypes and ultimately contribute to more personalized and effective therapies. Rapid advancement in the understanding of tumor biology as it exists in patients requires cooperation among institutions, surgeons, pathologists, cancer biologists and patients alike, primarily because this translational research is best done with patient-derived tissue grown in the xenograft setting as patient-derived xenografts. This review calls for a broader change in the approaches taken to study cancer pathobiology, highlights what implications the CSC paradigm has for pathologists and cancer biologists alike, and calls for greater collaboration between institutions, physicians and scientists in order to more rapidly advance our collective understanding of cancer.

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Identification of hematopoietic stem/progenitor cells: strength and drawbacks of functional assays

Cited by 99 publications

References 169 publications

Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells

Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells

The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation

Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

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