Abstract: In alternative embodiments, provided are methods for eradicating or reducing the in vivo numbers of cancer stem cells comprising administering to an individual in need thereof an ADAR1 (adenosine deaminase associated with RNA1) inhibiting agent, wherein the ADAR1 inhibiting agent reduces, or significantly reduces, ADAR1 Nano-luc reporter activity in cell lines and in human cancer stem cell assays. In alternative embodiments, provided are methods for inhibiting an RNA virus or a retrovirus, optionally a SARs-COV-2 virus, comprising lentiviral ADAR1 overexpression and in vivo administration, optionally intravenous (IV) administration, of a lentiviral ADAR1 transduced stem cell, optionally the stem cell is a cord blood CD34+ cell or a mesenchymal stromal cell.

Abstract: In alternative embodiments, provided are biosensing bioreactors that detect normal, pre-cancer and cancer stem cells. In alternative embodiments, provided are bioreactors for primary human hematopoietic stem and progenitor cell culture, manipulation and maintenance, which can comprise micro-peristaltic pumps to recapitulate blood flow. In alternative embodiments, provided are products of manufacture in the form of a bioreactor, or a nanobioreactor, or a customized cell culture bag with a defined three dimensional (3D) stromal microenvironment, and kits comprising them, and methods for making and using them. In alternative embodiments, the products of manufacture as provided herein, including the bioreactor, nanobioreactor, bag, customized cell culture bag and kits as provided herein, are used to and are capable of culturing, maintaining or supporting the culture of, and/or differentiating hematopoietic stem cells, including human hematopoietic stem cells, isolated from bone marrow or blood donors.

Abstract: In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Abstract: Provided herein, inter alia, are splice modulator compounds. The compounds include optically pure, stereospecific analogs of FD-895. The methods provided herein allow, for example, for scalable preparation of said compounds, and further allow, for example, use of said compounds for inhibiting spliceosome activity.

Abstract: In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Abstract: In alternative embodiment, provided are methods and compositions for treating, ameliorating or preventing diseases and conditions, such as cancer, including cancers associated with stem cells such as, without limitation, myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm like chronic myeloid leukemia (CML) or acute myeloid leukemia (AML), and ablating or killing cancer stem cells. In alternative embodiment, provided are a new set of biomarkers to detect leukemia stem cell reprogramming and CML progression. In alternative embodiment, provided are therapeutic targets for treating myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML) by targeting edited let-7 transcripts.

Abstract: In alternative embodiments, provided are methods for treating and ameliorating a cancer, or recurrence of a cancer such as acute myeloid leukemia (AML) comprising administration to an individual in need thereof a pharmaceutical composition comprising 17S-FD-895 (or rebecsinib) and second drug such as an ATP-competitive protein tyrosine kinase inhibitor such as dasatinib. In alternative embodiments, provided are methods for the in vivo inhibition of myeloproliferative neoplasm (MPN) or AML stem cell propagation comprising administration to an individual in need thereof a pharmaceutical composition comprising 17S-FD-895 and second drug. In alternative embodiments, provided are methods for the in vivo inhibition pre-leukemia stem cell (pre-LSC) transformation into leukemia stem cells (LSCs) comprising administration to an individual in need thereof a pharmaceutical composition comprising 17S-FD-895 and second drug.

Abstract: In alternative embodiments, provided are methods for treating and ameliorating a cancer such as a leukemia such as acute myeloid leukemia (AML) comprising administration to an individual in need thereof a pharmaceutical composition comprising imetelstat, or imetelstat and second drug such as dasatinib, or ruxolitinib, fedratinib, 8-aza-adenosine, raltegravir and/or dolutegravir or any combination thereof. In alternative embodiments, provided are methods for the in vivo inhibition of myeloproliferative neoplasm (MPN) or AML stem cell propagation comprising administration to an individual in need thereof a pharmaceutical composition comprising imetelstat, or imetelstat and second drug.

Abstract: In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Abstract: In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Abstract: The present disclosure provides methods of mitigating thiamine deficiency.

Abstract: Provided herein, inter alia, are splice modulator compounds. The compounds include optically pure, stereospecific analogs of FD-895. The methods provided herein allow, for example, for scalable preparation of said compounds, and further allow, for example, use of said compounds for inhibiting spliceosome activity.

Abstract: The present disclosure provides methods of mitigating thiamine deficiency.

Abstract: The present disclosure provides methods of mitigating thiamine deficiency.

Abstract: In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Abstract: In alternative embodiment, provided are methods and compositions for treating, ameliorating or preventing diseases and conditions, such as cancer, including cancers associated with stem cells such as, without limitation, myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm like chronic myeloid leukemia (CML) or acute myeloid leukemia (AML), and ablating or killing cancer stem cells. In alternative embodiment, provided are a new set of biomarkers to detect leukemia stem cell reprogramming and CML progression. In alternative embodiment, provided are therapeutic targets for treating myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML) by targeting edited let-7 transcripts.

Abstract: Methods and compositions are provided for the identification of stem cells and cancer stem cells. ?-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 ?-catenin, or members of the ?-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized ?-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.

Abstract: Methods, systems and kits are provided for the clinical staging of blood disorders including myelodysplastic syndrome, myeloproliferative diseases and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets. Additional functional, genetic, gene expression, proteomic or other molecular analyses of the hematopoietic stem and progenitor cells from the patients can also be employed in the staging methods of the invention.

Abstract: A method to prepare bone marrow or other hemopoietic cells free of malignant cells for autologous transplants is described. The mononuclear cells from the marrow are treated with a green porphyrin (Gp) to effect the uptake of said Gp by malignant cells selectively, and then irradiated with a wavelength of light absorbed by said Gp to effect the destruction of the malignant cells. The purged marrow cells can then be used for autologous transplantation.