61 results about "Lymphoblastic Leukemia" patented technology

The present invention relates to a system and a method for measuring and analyzing minimal residual disease (MRD) in pediatric B-cell precursor acute lymphoblastic leukemia (B-ALL) using multiparameter flow cytometry (MPFC). The invention finds application in clinical diagnostics and hematology-oncology for quantifying MRD in B-ALL patients with high sensitivity and specificity, needed for risk stratification, monitoring treatment response, and informing therapeutic decisions. The system comprises interconnected subsystems including an acquisition subsystem with an MPFC instrument, a control and file generation subsystem, and an analytical subsystem. The analytical subsystem incorporates modules for sequential data reduction, automated data cleaning, automated unsupervised data clustering, and interactive cluster analysis. Key advantages include high MRD detection sensitivity (e.g., 10⁻⁵ or 0.001%) and high specificity, without reliance on reference samples or supervised machine learning models, making it applicable in laboratories with different measuring equipment and using different panels of antibodies for identification of leukemic cells.

The present invention provides therapies for the treatment of CCR9 positive cancers, such as T cell acute lymphoblastic leukemia. In particular, the present invention provides a CCR9 targeting moiety. The invention also relates to a CCR9 targeting moiety comprising another targeting moiety, preferably a CD1a targeting moiety, to a dual CAR comprising CCR9 and CD1a targeting moieties, to the use thereof in the treatment of CCR9 and / or CD1a positive cancers, and to the use of a CCR9 targeting moiety and a CD1a targeting moiety alone for such treatments.

The invention provides a construction method and a construction system of a chronic lymphocytic leukemia prediction model based on machine learning, electronic equipment and a storage medium, and relates to the field of chronic lymphocytic leukemia prognosis research. The construction method comprises the steps of obtaining original sample data, and performing preliminary screening; performing data cleaning on the screened sample data; determining a prediction factor from the plurality of features of the cleaned sample data; dividing the cleaned sample data corresponding to the prediction factor and the target variable into a training set and a test set; inputting the training set after unbalance processing into a LightGBM model for training to obtain a prediction model; inputting the test set into a prediction model, performing hyper-parameter optimization on the prediction model, and evaluating the performance of the prediction model; calibrating the prediction model to obtain a calibrated prediction model; the method has the beneficial effects that the method can be realized only by depending on conventionally available predictive factors, and the patient screening can be realized before the CLL clinical symptoms appear.

The invention relates to an acute leukemia (ALL) high-throughput flow cytometry kit, and belongs to the field of leukemia detection.16 ALL cell antigens are added on the basis of an original 8-color flow cytometry, 24 antigens in the same cell can be detected at the same time, the detection precision of minimal residual focus (MRD) is greatly improved, and the detection sensitivity is improved. The ALL cells are divided into 12 developmental stages, so that immunological typing during primary diagnosis and immunophenotype variation after bone marrow transplantation and CAR-T cell treatment can be more accurately recognized, and the method has very important guiding significance on evaluation of treatment effects of patients and adjustment of treatment schemes.

The invention discloses a compound for targeted ubiquitination degradation of USP7 protein, and a medicinal composition and application thereof. The structural formula of the E3 ubiquitin ligase complex is as shown in formula I. A is a specific protein ligand in the E3 ubiquitin ligase complex; l is a bivalent linking group between a USP7 protein small molecule ligand and a specific protein ligand in an E3 ubiquitin ligase complex. The protein degradation chimera has the activity of inhibiting USP7 protein and the activity of degrading USP7 protein, and can effectively inhibit malignant proliferation of acute lymphatic leukemia cells, so that the protein degradation chimera can be used for related diseases with abnormal expression of USP7 protein.

The present study of the regulatory T phenotype of Sézary cells led to the discovery of the expression of GARP (LRRC32) by Sézary cells. GARP has also been shown to be overexpressed in samples from patients with acute lymphoblastic leukemia. GARP therefore appears as a diagnostic marker, for monitoring T-cell malignancies, and as a therapeutic target. Accordingly, the present invention relates to methods for the diagnosis and treatment of T-cell malignancies.

Monitoring active disease or progressive disease under therapy in chronic lymphocytic leukemia (CLL) represents a challenge to earlier and better adapt therapeutic strategy, notably in the era of targeted therapies in which minimal residual detection or mutations are sometimes not associated to poor clinical outcome. By following CLL patients before treatment (Binet stages A and B / C) or during targeted therapy, the Inventors developed a new flow cytometric method, based on CD69, CD49d, CD20 and CD279 expression at the surface of CD19+ / CD5+ B leukemic cells. Analyses of these markers alone or in combination show that CD69 / CD49d / CD20 / CD279 co-expression (quadruple population, QP) > 0.5% is the best criterion predicting CLL active disease or progression under therapy. This new flow cytometry immunophenotyping could help clinicians to monitor CLL evolution and quickly adapt their therapeutic strategy. Accordingly, the present invention relates to an ex vivo method for predicting active Chronic Lymphocytic Leukemia (CLL) or progressive CLL under therapy in a subject suffering from CLL, comprising the step of quantifying a population of CD69+ / CD49d+ / CD20+ / CD279+ cells in a sample obtained from the subject.

In one aspect, the disclosure relates to composition and methods for proteolysis-targeting chimeric molecules (PROTACs). In some aspects, the disclosed compounds are useful for modulating LCK tyrosine kinase activity through targeted degradation. In some aspects, the disclosed compounds are orally bioavailable. In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using the same, such as T-cell acute lymphoblastic leukemia. 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 disclosure.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma, or myelodysplastic syndrome by administration of Compound (I): (I), or a pharmaceutically acceptable salt thereof.

Disclosed are novel compounds for use in treating a proliferative disorder such as a cancer. Further disclosed are compositions comprising the novel compounds. Methods of using the disclosed compounds and compositions are further described. The methods include administering one or more of the disclosed compounds for treatment of various proliferative disorders, including an HRAS-driven cancer, a KRAS-driven cancer, a NRAS-driven cancer, Ewing sarcoma, B-cell acute lymphoblastic leukemia, leukemia, lung cancer, non-small cell lung cancer (NSCLC), solid tumor, breast cancer, triple-negative breast cancer (TNBC), hormone-resistant triple negative breast cancer. Further described are combination therapies in which a novel compound is administered in combination with one or more of a MEK inhibitor, a KRAS G12C inhibitor, or a Selective Estrogen Receptor Degrader (SERD) to an individual in need thereof.

Therapeutic combinations of an AKT inhibitor and a BCL-2 inhibitor; an AKT inhibitor and a glucocorticoid; and an AKT inhibitor, a BCL-2 inhibitor and a glucocorticoid are described. The combinations can be useful in the treatment of acute lymphoblastic leukemia (ALL).

The present invention relates to a novel anti-HLA-DR IgM isotype monoclonal antibody and to the use thereof alone or in addition to anti-CD20 IgG1 or IgM isotype antibodies, in the treatment of B-phenotype lymphoid hemopathies, and in particular of non-Hodgkin lymphoma B, chronic lymphocytic leukemia (CLL) and B-cell malignant lymphoid hemopathies in general.

Provided is a pharmaceutical combination comprising an antibody specific for CD19 and a natural killer cell, and a treatment method using the same. Such a pharmaceutical combination is capable of exhibiting synergistic therapeutic effects on a malignant tumor of B-cell origin such as non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and / or acute lymphoblastic leukemia.

Provided herein are methods of treating diseases (e.g., proliferative disease (e.g., cancer (e.g., breast cancer, colon cancer, testicular cancer, CNS cancer, stomach cancer, lymphoma (e.g., B-cell lymphoma (e.g., lymphoplasmacytic lymphoma (e.g., IgM secreting lymphoplasmacytic lymphoma (i.e., Waldenstrom's Macroglobulinemia), non-IgM secreting lymphoplasmacytic lymphoma)), diffuse large B-cell lymphoma (e.g., activated B-cell-like (ABC)-DLBCL, germinal center B-cell-like (GBC)-DLBCL), follicular lymphoma, marginal zone B-cell lymphoma, small lymphocytic lymphoma, mantle cell lymphoma), and leukemia (e.g., chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia, myelogenous leukemia (e.g., chronic myelogenous leukemia, acute myelogenous leukemia))))) comprising administering to the subject in need thereof a therapeutically effective amount of Compound (I). Further provided are methods for treating disease resistant to treatment with BTK inhibitors (e.g., ibmtinib). Formula (I)

Disclosed is L-asparagine aminohydrolase and polyethylene glycol conjugate. The polyethylene glycol has a molecular weight less than or equal to about 5000 Da and the protein is an L-asparaginase from Erwinia. The conjugate has a high level of in vitro activity and an unexpected increase in half-life in vivo. Methods of producing the conjugate and methods of using the conjugate in therapy in treatment of cancer, particularly Acute Lymphoblastic Leukemia (ALL). The method is disclosed for use of the conjugate as a second line therapy for patients who have developed hypersensitivity or have had a disease relapse after treatment with other L-asparaginase preparations.

The invention provides application of chidamide or a derivative thereof in preparation of a medicine for preventing and / or treating acute T lymphocytic leukemia. According to statistics of curative effect data of grouped clinical patients, compared with an existing treatment scheme (the curative effect is 20-30%) for treating acute T-ALL, the pharmaceutical composition provided by the invention has the advantages that the curative effect can be improved to 75%, and remarkable clinical benefits are brought.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma, or myelodysplastic syndrome by administration of Compound (I): (I), or a pharmaceutically acceptable salt thereof.

Relapsed / refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. CD1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD1a during ontogeny, confining the risk of on-target / off-tumor toxicity. The present invention provides CD1a-targeting moieties comprising a CD1a-which may be placed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.

The application discloses a kind of nano-drugs for treating T-ALL by combining aptamer sgc8 delivery siBCL11B and preparation method and application.The application takes acute T-cell lymphoblastic leukemia cell Molt4, CCRF-CEM as research object, and the nano-drugs are delivered by in-vitro drug addition experiment etc., and the viability and apoptosis of cell are determined.The results show that the nano-drugs can effectively and stably transfect and deliver siBCL11B into T-ALL tumor cell strain and successfully release siBCL11B, knock down the expression of BCL11B in T-ALL cell strain, thereby promoting the apoptosis of tumor cell strain and inhibiting the viability of tumor cell strain.Based on the results, the nano-drugs can be used for delivering siBCL11B and thereby used for the clinical treatment of acute T-cell lymphoblastic leukemia.

Heterocyclic compounds, their stereoisomers and their pharmaceutically acceptable salts are useful in the treatment of many types of cancers, such as cancers of the breast, prostate, pancreatic, gastric, lung, colon, rectum, esophagus cancer, duodenum, tongue, pharynx, liver, kidney, bile duct, uterine body, cervix, ovaries, urinary bladder, and skin. Other cancers to be treated include brain tumor, neurinoma, clear cell carcinoma, non-small cell lung cancer, small cell lung cancer, hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bone tumor, vascular fibroma, glioblastoma, Neuroblastoma, sarcoma, neuroendocrine tumors, retinoblastoma, penile cancer, pediatric solid cancer, renal cell carcinoma, lymphoma, myeloma, leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, cutaneous T-cell lymphoma (CTCL), multiple myeloma (MM), myeloproliferative neoplasms (MPN), Myelodysplastic syndrome (MDS), polycythemia vera (PV), essential thrombocythemia, essential thrombocytosis (ET), and myelofibrosis (MF), and also including their metastases.

Recombinant receptors with a binding domain that binds B cell activation factor receptor (BAFF-R) are disclosed. Recombinant receptors include chimeric antigen receptors (CAR) having an anti-BAFF-R binding domain, a transmembrane domain, a CD3ζ / 4-1BB intracellular signaling domain, and a spacer. Methods and systems to treat BAFF-R-expressing cancers, such as mantle cell lymphoma (MCL), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL), are also provided. The recombinant receptors disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

A compound for degrading USP7 protein by means of targeted ubiquitination, a pharmaceutical composition thereof and the use thereof. The structural formula thereof is shown as formula (I), wherein A is a specific protein ligand in an E3 ubiquitin ligase complex, and L is a divalent linker group between a small molecule ligand of the USP7 protein and the specific protein ligand in the E3 ubiquitin ligase complex. The protein degradation chimera has both USP7 protein inhibitory activity and USP7 protein-degrading activity, can effectively inhibit malignant proliferation of acute lymphoblastic leukemia cells, and thus can be used for diseases associated with abnormal USP7 protein expression.

The present disclosure relates to anti-SAA antibodies or fragments thereof, such as antibodies against human SAA1 or fragments thereof, that may be used in various therapeutic, prophylactic and diagnostic methods. The present antibodies or fragments thereof may be used to treat hematologic disorders such as acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome.

The invention belongs to the field of medical treatment, and discloses an application of 11-MT in medicine preparation. The medicine refers to a medicine for treating acute B lymphocytic leukemia. Researches show that 11-MT shows the following advantages in treatment of acute B lymphocytic leukemia: in an in-vitro test, 11-MT significantly promotes apoptosis of BALL-1 cells and shows dose dependence, 11-MT significantly promotes generation of ROS in the BALL-1 cells and shows dose dependence, 11-MT can cause DNA damage of the BALL-1 cells and shows dose dependence, and in an in-vivo test, 11-MT can significantly promote apoptosis of the BALL-1 cells and shows dose dependence. The 11-MT has a regulating effect on specific organ lesions, shows good repairing and protecting effects, can recover multiple serum biochemical indexes abnormally increased due to tumor load to a normal level, and can well reduce tumor cell infiltration.

The present disclosure provides methods of treating acute myeloid leukemia (AML) and determining responsiveness to an AML treatment regimen, which methods involve identifying the presence or absence of myeloid / lymphocytic leukemia stem cells (M / L LSCs) in a sample from a subject.

The present disclosure provides methods for treating Philadelphia chromosome positive (Ph +) leukemia, such as CML (chronic myeloid leukemia, chronic myeloid leukemia, chronic myeloid SOS-1 inhibitors (such as bicyclic or macrocyclic compounds) of Ph + ALL (acute lymphoblastic leukemia), Ph + AML (acute lymphoblastic lymphoma), alone or in combination with TKI (such as dasatinib or imatinib) against BCR-ABL tyrosine kinases are disclosed.

Novel chimeric and / or humanized forms of the anti-CD45 BC8 antibody are described. The disclosed chimeric or humanized antibodies can be used as research, diagnostic, or therapeutic tools against CD45-related disorders, such as hematologic malignancies including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), other myeloid and lymphoid disorders, other cancers, as well as non-malignant disorders, such as autoimmune disorders, infections, inherited blood disorders, and metabolic disorders.

The present application relates to a kind of acute leukemia (ALL) high flux flow detection kit, belong to leukemia detection field, the present application is based on the original 8 color flow to increase 16 kinds of ALL cell antigen, can realize the simultaneous detection of 24 kinds of antigens in the same cell, not only greatly improve the detection precision of micro residual lesion (MRD), and by being divided into 12 development stages to ALL cell, can more accurately identify immunotyping when first diagnosis, and immunophenotypic aberration after bone marrow transplantation and after CAR-T cell therapy, this has very important guiding significance to the evaluation of patient treatment effect and the adjustment of treatment scheme.

The present invention relates to a reagent panels for the measurement of minimal residual disease (MRD) associated with pediatric B-cell precursor acute lymphoblastic leukemia (B- ALL) by multiparametric flow cytometry. The reagent panel of the invention comprises a combination of antibodies directed against markers, wherein the combination of antibodies comprises i) antibodies targeting markers CD45, CD20, CD34, CD38, CD10, CD58, CD66c, CD73, CD81, CD123, CD304, CD44, CD86, CD99 and CD371, and ii) antibodies targeting markers CD19 and / or CD22, wherein the antibodies are conjugated with fluorochromes. The invention further relates to the use of said panels for detecting MRD associated with B-ALL and / or for identifying a subject at risk of developing B-ALL relapse. The invention also relates to methods of detecting MRD associated with B-ALL. Key advantages of the invention include achieving high MRD detection sensitivity (e.g., 10⁻⁵ or 0.001%) and high specificity.