Abstract: The present disclosure provides compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK) (e.g., Janus kinase 2 (JAK2)) and/or cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 11 (CDK11)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.

Abstract: The present disclosure provides compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK) (e.g., Janus kinase 2 (JAK2)) and/or cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 11 (CDK11)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.

Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Disclosed are bispecific compounds (degraders) that target ITK or a zinc finger (ZnF) protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by ITK or ZnF protein activity.

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, cocrystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, cocrystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Aspects of the application relate to methods and systems for evaluating treatment response by measuring treatment-induced changes at the single cell level. The disclosure provides methods for isolating single cells that are primary cancer cells, including primary cancer cells from solid tumors, and detecting in minutes to hours from their removal from the body the response of such cells to anti-cancer agents such as radiation, small molecules, biologies, DNA damaging agents and the like.

Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof or any combination thereof.

Abstract: A method of rapid functional analysis of cells is provided. A body fluid sample is introduced into a reservoir of a measurement instrument. A living cell is loaded directly from the body fluid sample into a channel of the measurement instrument in the absence of long-term cell culturing, cell passaging, and application of long-term drug pressure to cells. A functional biomarker of the living cells is measured while the living cell flows through the channel. The functional biomarker measured may be mass accumulation rate (MAR) or mass change. The measurement instrument may be a suspended microchannel resonator (SMR).

Abstract: The invention provides methods for evaluating disease, such as cancer, by way of performing multiple assays involving single-cell analysis on live cells isolated from a sample of a patient. The data obtained from the multiple assays is analyzed and linked to thereby provide a characterization of any given cell having undergone analysis, which, in turn, allows for evaluation of the sample either known to be, or suspected of being, cancerous. A report may be generated based on the data analysis, wherein the report provides information related to the cancer evaluation, including, but not limited to, whether the sample tested positive for cancer, a determination of a stage or progression of cancer, and a customized treatment plan tailored to an individual patient's cancer diagnosis.

Abstract: Patient samples are monitored to detect minimal residual disease (MRD) post successful cancer treatment. Upon detection of MRD, functional assays can be performed on living cancer cells from the patient to evaluate possibly effective therapies along with subsequent genomic or other more destructive assays to provide additional efficacy information using a single sample. An effective treatment against the MRD can be identified and selected for the patient. The patient can be monitored and the process repeated until MRD can no longer be detected.

Abstract: The present invention relates to methods for identifying, assessing, preventing, and treating cancer (e.g., lymphoid and/or myeloid malignancies such as B-ALL in humans). A variety of histone H3K27rne3 biomarkers are provided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers is associated with cancer status and indicates amenability to treatment or prevention by modulating H3K27me3 levels. The present invention further relates to methods of increasing the number of lymphoid progenitor cells (e.g., increase self-renewal and cell proliferation) by contacting the lymphoid progenitor cells (e.g., wild type and/or genomically altered cells) with an agent that inhibits polycomb repressor complex 2 (PRC2) activity or reduces H3K27roe3 levels.

Abstract: The invention relates to cytokine receptor-like factor 2 (CRLF2), and particularly certain mutant forms of CRLF2, as prognostic and therapeutic targets in precursor B-cell acute lymphoblastic leukemia (B-ALL). Mutant CRLF2 with a Phe232-Cys (F232C) mutation is overexpressed and constitutively activates STAT5 in a subset of B-ALL patients with particularly poor prognosis. Methods and compositions useful for identifying, inhibiting expression, and inhibiting activity of the mutant CRLF2 are provided. Also provided are methods and compositions useful for treating B-ALL.