Leland Stanford Junior University

Laurie Elizabeth Ailles

Irving L Weissman

Catriona Helen M Jamieson

Tannishtha Reya

Michael F Clarke

Karl G Sylvester

Monika Tataria

Squamous carcinoma stem cells (SCSC) are identified. The cells can be prospectively isolated or identified from primary tumor samples, and are shown to possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation, and to form unique histological microdomains useful in cancer diagnosis.

Identification and isolation of squamous carcinoma stem cells

Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the &#x3b2;-catenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.

Methods for phenotyping of leukemias

Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the bcatenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.

Identification, isolation and elimination of cancer stem cells

Methods and compositions are provided for the identification of stem cells and cancer stem cells. &#x3b2;-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at &#x3b2;-catenin, or members of the &#x3b2;-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized &#x3b2;-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.

Methods of identifying and isolating stem cells and cancer stem cells

Methods and compositions are provided for the identification and isolation of mammalian mesenchymal stem cells. The methods of the invention provide a means to obtain substantially homogeneous MSC populations. In some embodiments, the homogeneous MSC composition is stable in non-differentiating culture conditions, where the proportion of cells in the composition that have an MSC phenotype are maintained over multiple passages.

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Stanford, CA, United States of America

Laurie Elizabeth Ailles