51 results about "Myeloid hyperplasia" patented technology

The invention relates to methods of treating functional iron deficiency (FID) associated with low, very low, or intermediate risk myelodysplastic syndromes. FID associated with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF), and FID associated with myelodysplastic syndromes / myeloproliferative neoplasm (MPN) overlap syndromes using small molecule ALK2 inhibitors.

The present disclosure is concerned with compounds and compositions for use in the prevention and treatment of cancer associated with FBOX21 mediated p85a ubiquitination such as, for example, cancer (e.g., sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, a glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, non-small cell lung carcinoma, renal cancer, lung cancer, colon cancer, cervical cancer, and plasma cell neoplasm (myeloma)). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Disclosed herein are methods for using an antimalarial endoperoxide compound, such as artemisinin, in treating a subject suffering from myelodysplastic syndromes (MDS), and in slowing or preventing the progression of MDS in the subject to development of acute myeloid leukemia (AML).

The present disclosure relates to 4'-thio-nucleotides and nucleoside compounds for the treatment of various cancers, such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative tumors and plasma cell neoplasms (myeloma). The abstract is intended to be a scanning tool for the purpose of searching in a specific field and is not intended to limit the present invention.

The present invention provides a method for treating or inhibiting a myeloproliferative tumor (MPN) in a subject in need thereof, the method comprising administering to the subject a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) and one or more Jak inhibitors and / or one or more hypomethylating agents.

Therapeutic methods and pharmaceutical compositions for treating a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis, are described. In certain embodiments, the invention includes therapeutic methods of treating a MPN using a combination of a compound of Formula (I) or Formula (II) with a therapeutic agent selected from the group consisting of a JAK inhibitor, an IDH inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, an interferon, a PI3K inhibitor, an AKT inhibitor, an mTOR inhibitor, a nucleoside analog, and combinations thereof.

Methods and compositions disclosed herein generally relate to compositions and methods for suppressing hematopoietic stem and progenitor cells (HSPCs) and the treatment of diseases or disorders involving UBE2N, such as cancers, including disorders such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and chronic inflammatory disorders. Particular aspects relate to treating, e.g. acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5). Particular aspects of the invention relate to determining an individual in need of treatment who can be treated with a UBE2N inhibitor, such as an individual having AML-M4 and / or AML-M5. The invention further relates to using a UBE2N inhibitor to treat a disease or disorder characterized by malignant hematopoietic cells, as well as other cancers, and chronic inflammatory disorders, and as immune checkpoint regulators.

The present invention relates to pharmaceutical agents useful for therapy and / or prophylaxis in a mammal, pharmaceutical composition comprising such compounds, and their use as menin / MLL protein / protein interaction inhibitors, useful for treating diseases such as cancer, including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN); and diabetes.

Described herein are certain quinoline carboxamides for use in the treatment of myeloproliferative tumors (MPNs). Said quinoline carboxamides, optionally in combination with an additional compound selected from the group consisting of Janus kinase (JAK) inhibitors, bromodomains and terminal exo-motif protein (BET) inhibitors, B cell lymphoma 2 (Bcl-2) inhibitors, and combinations thereof, can more specifically be used for the treatment of advanced MPNs, including accelerated MPNs and secondary acute myeloid leukemia, such as acute myeloid leukemia. , acute myelogenous leukemia evolved from a previous myeloproliferative tumor (AML after MPN). Also included are pharmaceutical combinations of the quinoline carboxamide and a second agent, such as a BET inhibitor or a Bcl-2 inhibitor. Also included are certain quinoline carboxamides for use in the treatment of myeloproliferative tumors (MPN) in combination with a BET inhibitor or a Bcl-2 inhibitor.

The present disclosure provides a method of treating an inflammatory disease or disorder, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) in a subject, the method comprising administering to the subject a compound that inhibits IRAK1 and IRAK4. The present disclosure further provides a method of determining a subject with a disease / disorder that can be treated by the administration of a compound which inhibits IRAK1 and IRAK4.

There is described herein a method of prognosing or classifying a subject with a Myeloproliferative Neoplasm (MPN) comprising: (a) determining the expression level of at least 10 genes in a test sample from the subject selected from the group consisting of SPP1, CEACAM6, GJA1, IGSF10, IGFBP2, COL4A5, LYVE1, MTIE, EMP1, XIST, DLK1, TPSAB1, TIMP3, CLC, MS4A1, ENKUR, ALOX12, KNDC1, HLA-DQB1, GAS2, CLEC2L, BEND2, CDH7, and NT5E; and (b) comparing expression of the at least 10 genes in the test sample with reference expression levels of the at least 10 genes from control samples from a reference cohort of patients; wherein a difference or similarity in the expression of the at least 10 genes in the test sample and the reference expression levels is used to prognose or classify the subject with MPN into a low risk group or a high risk group for worse survival.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

A diagnostic, preventive, or therapeutic agent may be used for a myeloproliferative neoplasm. An antibody or a functional fragment thereof that binds to a cleaved mutant CALR protein, may include an antigen-recognition site in (a) a polypeptide chain having an amino acid sequence set forth in SEQ ID NO: 1 or (b) a polypeptide chain having an amino acid sequence having deletion, substitution, or addition of one to several amino acids in SEQ ID NO: 1; and a diagnostic, preventive, or therapeutic agent for a myeloproliferative neoplasm containing the antibody.

Antibodies and antigen-binding fragments thereof that bind to type II transmembrane serine protease 6 (TMPRSS6) on the surface of a cell and increase hepcidin expression are provided, as well as methods of using the anti-TMPRSS6 antibodies and fragments for the treatment of iron metabolism disorders and myeloproliferative disorders.

The present invention relates to pharmaceutical agents useful for therapy and / or prophylaxis in a mammal, pharmaceutical composition comprising such compounds, and their use as menin / MLL protein / protein interaction inhibitors, useful for treating diseases such as cancer, including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproiiferative neoplasms (MPN); and diabetes.

Disclosed herein are crystalline polymorphs of indotecan (LMP400) that can be used in the treatment of cancers associated with dysregulation of Topl and / or MYC activity, such as, for example, a sarcoma, (e.g., Ewing's sarcoma), a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, a melanoma, a. glioma, leukemia, a lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mll2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modelled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic dells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Disclosed herein are crystalline polymorphs of LMP744 that can be used in the treatment of cancers associated with dysregulation of Top1 and / or MYC activity, such as, for example, a sarcoma, (e.g., Ewing's sarcoma), a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, a melanoma, a glioma, leukemia, a lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). This abstract is intended as a scanning tool for purposes of searching m the particular art and is not intended to be limiting of the present invention.

This application relates to the field of medicinal chemistry, specifically to cyclopropanamide-containing compounds represented by formula (I) and their uses, which have great medical value and market potential for autoimmune diseases and myeloproliferative neoplasms. [Formula 1] TIFF2025501662000047.tif33170

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Provided according to embodiments of the invention are methods of treating a disorder in a subject in need thereof that include administering to the subject an effective amount of cedazuridine, an effective amount of decitabine, and an effective amount of venetoclax, thereby treating the disorder in the subject. In some embodiments of the invention, the disorder is a hyperproliferative disorder such as a cancer. In some embodiments, the disorder is a hematological cancer such as myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), leukemia (e.g., acute myeloid leukemia), or lymphoma.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mll2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modelled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic dells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express cytotoxic chimeric receptors and various dosing regimens for administering such cells. In several embodiments, the immune cells express a chimeric receptor that targets ligands of NKG2D on tumor cells. In several embodiments, the cancer is a blood cancer, for example, acute myeloid leukemia (e.g., relapsed / refractory acute myeloid leukemia) or myelodysplastic syndrome. In several embodiments, the tumor is a solid tumor, for example, intrahepatic cholangiocarcinoma or other liver tumor, for example, secondary metastases from colorectal cancer.

The invention provides, inter alia, a CTPS1 inhibitor for use in the treatment of a myeloproliferative neoplasm (MPN) in a human subject.

The present invention relates to a pharmaceutical composition for subcutaneous injection comprising anagrelide, 3-hydroxyanagrelide, or a pharmaceutically acceptable salt thereof, comprising a hydrochloride thereof, in a solvent comprising a medium chain triglyceride (MCT) oil and optionally ethanol. The invention also relates to methods for preparing these pharmaceutical compositions and dosage forms, and methods of treating subjects having cancer or myeloproliferative disorders using the pharmaceutical compositions and dosage forms provided herein.

Compositions and methods for treatment of conditions associated with IDH1 / 2 mutation(s) are disclosed. The compositions and methods include administering an SRC inhibitor and a p70 S6 kinase / AKT (S6K / AKT) inhibitor. Examples of conditions associated with IDH1 / 2 mutation(s) include intrahepatic cholangiocarcinoma (ICC), oligodendrogliomas, astrocytomas, glioblastomas, leukemias, adenocarcinoma, gliomas, melanomas, oligoastrocytomas, invasive breast carcinoma, invasive ductal carcinoma, and myelodysplastic syndromes.

Aspects of the disclosure include methods for treating a myeloproliferative neoplasm. Methods according to certain embodiments include co-administering to a subject a Janus kinase (JAK) inhibitor and a telomerase inhibitor comprising an oligonucleotide and a lipid moiety linked to the 5′ and / or 3′ end of the oligonucleotide. Methods for inducing apoptosis of a myeloproliferative neoplasm cell by contacting the cell with an amount of a JAK inhibitor and a telomerase inhibitor sufficient to induce apoptosis are also described. Compositions having a JAK inhibitor and a telomerase inhibitor for practicing the subject methods are also provided.

Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.

Aspects of the disclosure include methods for treating a myeloproliferative neoplasm. Methods according to certain embodiments include co-administering to a subject a Janus kinase (JAK) inhibitor and a telomerase inhibitor comprising an oligonucleotide and a lipid moiety linked to the 5′ and / or 3′ end of the oligonucleotide. Methods for inducing apoptosis of a myeloproliferative neoplasm cell by contacting the cell with an amount of a JAK inhibitor and a telomerase inhibitor sufficient to induce apoptosis are also described. Compositions having a JAK inhibitor and a telomerase inhibitor for practicing the subject methods are also provided.