Normal and leukemic hematopoiesis: Are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?

Passegué, Emmanuelle; Jamieson, Catriona; Ailles, Laurie; Weissman, Irving L.

doi:10.1073/pnas.2034201100

Cited by 582 publications

(480 citation statements)

References 104 publications

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“…They are similar to stem cells and are capable of both self-renewal and differentiation into all of the cells within a tumor (Siclari and Qin, 2010;Rangwala et al, 2011). CSCs have been identified in a number of cancers including acute myeloid leukaemia (AML) (Bonnet and Dick, 1997;Passegue et al, 2003), glioblastoma (Singh et al, 2003), breast (Al-Hajj et al, 2003;Ponti et al, 2005), lung (Kim et al, 2005), prostate (Collins et al, 2005), ovarian (Bapat et al, 2005), gastric (Houghton et al, 2004), esophagous ( Li et al, 2013 ), Head and Neck SCC (Satpute et al, 2013) and skin cancers (Frank et al, 2005;Monzani et al, 2007). Different markers have been identified to be expressed on melanoma stem cells (Quintana et al, 2010;Shakhova and Sommer, 2013) comprising CD20 (Fang et al, 2005) and ABC transporter family members such as MDR1, ABCG2 and ABCB5 (Frank et al, 2003;Frank et al, 2005;Monzani et al, 2007;Keshet et al, 2008;Schatton et al, 2008), CD271 (Boiko et al, 2010;Civenni et al, 2011), CD44 (Fernandez-Figueras et al, 1996, CD133 (Klein et al, 2006) and Nestin (Piras et al, 2010;Fusi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

Sabet¹,

Rakhshan²,

Erfani³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Introductionmentioning

confidence: 99%

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

Sabet¹,

Rakhshan²,

Erfani³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…2 It has been found that mutations occurring during expansion phases of totipotential stem cells throughout development may prompt the formation of tumors in adulthood. In mature adult tissues, stem cells and progenitor cells may also constitute the sources of oncogenic transformation following somatic mutations, as shown by the isolation of TSCs from human acute myeloid leukemia (AML) [3][4][5][6] and breast cancer. [7][8][9] In tumors of the central nervous system (CNS), TSCs have also been isolated and successfully maintained in culture from medulloblastoma, 10 glioblastoma, [11][12][13][14][15][16][17][18] and ependymoma, 19 as well as from several glioma cell lines.…”

mentioning

confidence: 99%

Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma

Zhou

Ping

et al. 2007

Modern Pathology

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A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis of this unique type of tumor and assist in the design of novel therapeutic strategy. Here, tumor stem cell-like precursors were identified from primary human anaplastic oligoastrocytomas by labeling of the tumor sections with nestin and CD133. Tumor cells were cultured in vitro in stem cell medium with growth factors and the capacity of the surviving stem cell-like precursors to form tumor spheres was tested. The tumor spheres were further injected subcutaneously into nude mice to observe the contribution of stem cell-like precursors to histological composition and tumor progression. We found that primary human oligoastrocytoma tissues contained nestin þ /CD133 þ stem cell-like precursors. These cells differentiated into tumor cells with both oligodendroglial and astrocytic characteristics and formed tumor spheres in vitro, which upon implantation in nude mice, grew into tumor nodules containing nestin þ /CD133 þ cells at levels higher than in the primary tumor tissues. This study revealed for the first time that anaplastic human oligoastrocytomas contained stem cell-like precursors, which exhibit neural stem cell properties with tumorigenicity. These stem cell-like precursors may be responsible for the oligodendroglial and astrocytic components of human oligoastrocytoma and should be considered as therapeutic targets.

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“…4 Leukemic transformation disrupts this balance favoring proliferation over differentiation, but the mechanisms underlying cell cycle regulation and checkpoint control in the hematopoietic system are not understood. 5 Recent data from our laboratory has identified a unique role for the Rb tumor suppressor gene in the response to anemic and oxidative stress 6 that has implications not just for red cell production but for the homeostatic balance in the entire hematopoietic system and for the development of hematopoietic malignancies. …”

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confidence: 99%

The Rb Tumor Suppressor in Stress Responses and Hematopoietic Homeostasis

Macleod¹

2004

Cell Cycle

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The Rb tumor suppressor pathway is functionally inactivated in most human cancers. 1 In human blood cancers, loss of Rb expression has been widely reported in both acute myeloblastic and acute lymphoblastic leukemias, cyclin D1 amplification is common in mantle cell lymphoma, and silencing of the p16/INK4a tumor suppressor gene occurs frequently in AML and various types of lymphoma. 2 Silencing of p16/INK4A expression is frequently caused by hyper-methylation of CpG islands in its promoter but may also be achieved through activation of Bmi-1, for example in lymphomas associated with the E2A-Pbx1 translocation. 3 Hematopoietic homeostasis ensures a balance between proliferation and differentiation at different levels within the hematopoietic hierarchy such that hematopoietic stem cell self-renewal, progenitor proliferation and terminal differentiation to functional blood cells are maintained throughout the life of the animal. 4 Leukemic transformation disrupts this balance favoring proliferation over differentiation, but the mechanisms underlying cell cycle regulation and checkpoint control in the hematopoietic system are not understood. 5 Recent data from our laboratory has identified a unique role for the Rb tumor suppressor gene in the response to anemic and oxidative stress 6 that has implications not just for red cell production but for the homeostatic balance in the entire hematopoietic system and for the development of hematopoietic malignancies. CRITICAL FUNCTIONS OF PRB IN STRESS ERYTHROPOIESISpRb is uniquely required for red blood cell production under stress conditions, such as anemia, following bone marrow transplantation, in the embryo and in mice with tumor burden in other tissues. 6 Under these conditions, Rb null erythroblasts fail to undergo normal growth arrest and instead accumulate with a 4N DNA content. 6 Rb null erythroblasts appear larger, have aberrant chromatin structure, express abnormally high levels of the transferrin receptor (CD71) and fail to enucleate. 6 These defects are cell autonomous and are not rescued by the presence of wild-type cells. 6,7 Erythroid enucleation is a poorly understood process that is regulated in vivo by critical interactions of the red cell with the extracellular matrix 8 and with other cells types, particularly macrophages. 9,10 Rb has been implicated in macrophage differentiation by promoting the activity of METS, a repressor of Ras induced proliferation and inhibitor of Ets mediated transactivation. 11 However, we continued to observe red cell proliferation and maturation defects in Rb null erythroblasts in chimeric bone marrow that contains wild-type macrophages, suggesting that the red cell defect is independent of potential macrophage abnormalities. 6 It is not yet clear whether the enucleation failure in Rb null red cells is a secondary consequence of abnormal cell cycle exit or whether it is caused by a distinct primary defect in red cell maturation under stress conditions. Colchicine treated erythroid cells can initiate enucleation from M ph...

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Normal and leukemic hematopoiesis: Are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?

Cited by 582 publications

References 104 publications

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma

The Rb Tumor Suppressor in Stress Responses and Hematopoietic Homeostasis

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