Abstract: Heterocyclic compounds of Formula I: and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed.

Abstract: The invention relates to compounds as described herein and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immunodeficient disease.

Abstract: Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed.

Abstract: It is provided a method of expanding ex vivo hematopoietic stem cells (HSC), the method comprising selecting a population of Endothelial Protein C Receptor (EPCR)+ HSC, culturing the selected HSC thereby expanding said EPCR+ HSC and the use of the expanded EPCR+ HSC for stem cells transplantation.

Abstract: The invention relates to compounds as described herein and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immunodeficient disease.

Abstract: It is provided the use of Pyrimido[4,5-B]indole derivatives as anti-cancer compounds, and more specifically the use of UM171 and its derivatives for treating cancer, by activating the CULLIN3-RING ubiquitin ligase complex which degrades RCOR1 which normally acts as the scaffolding protein for the RCOR1/LSD1 and HDAC2 complex, itself being dissociated in the presence of UM171. Thus UM171 acts like a molecular glue degrader, inhibiting HDACs, RCOR1, CoREST and LSD1 and resulting in an anti-cancer activity.

Abstract: Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed.

Abstract: It is provided a method of expanding dendritic (DC) cells and/or natural killer (NK) cells in vivo in a patient comprising the steps of producing a graft of stem and progenitor cells cultured with UM171 or analogues therefrom and expanded before being administered to the patient. The expansion or increase in dendritic (DC) cells and/or natural killer (NK) cells population in the patient results in an increase immune response reducing transplant related mortality (TRM), severe graft-versus-host disease (GVHD), relapse, and/or severe viral infections.

Abstract: The invention relates to compounds as described herein and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immunodeficient disease.

Abstract: A method for treating acute myeloid leukemia (AML), such as poor risk AML, by administering to a subject in need thereof an effective amount of a mitochondrial activity inhibitor, for example a class A electron transport chain (ETC) complex I inhibitor such as Mubritinib or a pharmaceutically acceptable salt thereof, is disclosed. The AML to be treated may be characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDII1, mutated IDII2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Abstract: Compounds of general formula or salts or prodrugs thereof, are provided and described herein. The compounds are useful to expand hematopoietic stem cell and/or hematopoietic progenitor cell populations. Particularly, the hematopoietic cells are human cells. The compounds are also useful in the medical treatment of hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immune-deficient disease in a subject.

Abstract: Pyrimido[4,5-b]indole derivatives are provided. These compounds are useful to expand hematopoietic stem cell populations, particularly, human hematopoietic stem cell populations. The compounds are also useful in the medical treatment of diseases that involve hematopoietic stem cells.

Abstract: A method for treating acute myeloid leukemia (AML), such as poor risk AML, by administering to a subject in need en thereof an effective amount of a mitochondrial activity inhibitor, for example a class A electron transport chain (ETC) complex I inhibitor such as Mubritinib or a pharmaceutically acceptable salt thereof, is disclosed. The AML to be treated may be characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT 1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Abstract: Methods and compositions for enhancing viral gene transfer, such as lentiviral gene transfer, and improving the efficacy of gene delivery to cells such as primitive hematopoietic cells, are described. These methods and compositions are based on the use of pyrimido[4,5-b]indole derivatives. Cell-based compositions and methods useful for therapeutic indications amenable to treatment with gene therapies, including hematopoietic stem cell therapies, are also described.

Abstract: It is provided a method of expanding ex vivo hematopoietic stem cells (HSC), the method comprising selecting a population of Endothelial Protein C Receptor (EPCR)+ HSC, culturing the selected HSC thereby expanding said EPCR+ HSC and the use of the expanded EPCR+ HSC for stem cells transplantation.

Abstract: Methods and compositions for enhancing viral gene transfer, such as lentiviral gene transfer, and improving the efficacy of gene delivery to cells such as primitive hematopoietic cells, are described. These methods and compositions are based on the use of pyrimido[4,5-b]indole derivatives. Cell-based compositions and methods useful for therapeutic indications amenable to treatment with gene therapies, including hematopoietic stem cell therapies, are also described.

Abstract: Methods and kits for the diagnosis and prognosis of acute myeloid leukemia (AML) are described. These methods and kits are based on the assessment of the level of expression of the gene High Mobility Group AT-hook 2 (HMGA2), and optionally of the level of expression of at least one additional prognostic marker gene such as PRKC Apoptosis WT1 Regulator (PAWR), in a biological sample from an AML patient. High levels of expression of HMGA2 and PAWR in the sample are associated with poor disease prognosis, for example low probability of survival and/or increased risk of relapse, in AML patients, including in intermediate-risk AML patients. Methods and kits for the diagnosis of AMLs with TP53 mutations based on genes differentially expressed in AMLs with TP53 mutations relative to other AMLs also described.

Abstract: Pyrimido[4,5-b]indole derivatives are provided. These compounds are useful to expand hematopoietic stem cell populations, particularly, human hematopoietic stem cell populations. The compounds are also useful in the medical treatment of diseases that involve hematopoietic stem cells.

Abstract: Genes exhibiting specific mutational and/or transcriptional patterns in poor prognosis AMLs, such as EVI1-rearranged acute myeloid leukemias (EVI1-r AMLs), relative to other types of AMLs and/or normal CD34+ cells, are disclosed. The use of these mutational and/or transcriptional patterns, for example the expression level of the PRKC Apoptosis WT1 Regulator (PAWR) gene, for the diagnosis or prognosis of AMLs, including intermediate-risk AMLs, is also disclosed.

Abstract: Novel methods for modulating acute myeloid leukemia stem/progenitor cell expansion and/or differentiation are disclosed. These methods are based on the use of aryl hydrocarbon receptor (AhR) modulators and/or compounds of formula I or II Screening assays to identify compounds that may be useful for inhibiting and/or eliminating AML initiating cells using AhR modulators and/or the compounds of formula I or II are also disclosed. The use of pharmaceutically acceptable agonists of the AhR for preventing or inhibiting minimal residual disease (MRD) in an AML patient is also disclosed.