57 results about "Leukaemia cell" 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 invention relates to a management method and system for a leukemia cell morphology intelligent recognition microscopic device, and solves the problems that imaging quality fluctuates, suspicious cell recognition precision is limited, and clinical efficient standardization requirements are difficult to meet. Extracting sample features and calling a parameter library according to rules to select optimal scanning and imaging parameters for initialization; starting an X / Y-axis motor according to the parameters, and correcting the deviation by combining an anti-interference rule and an encoder; z-axis dual-stage focusing is carried out after stable stopping, and an FPGA time sequence control camera carries out acquisition; aI judgment results are sent to images, suspicious cells are delineated and then positioned, and high-power lens re-focusing collection and AI recognition are carried out. The method has the advantages that sample adaptation and positioning precision is improved, suspicious cell recognition is optimized, and detection efficiency and precision are improved.

The application discloses a kind of trichoderma fermentation processing indigo blue method, the product obtained and application.The method includes: preparation trichoderma seed liquid;After primary indigo blue sterilization, access seed liquid, fermentation 5-9 days under 25-30 DEG C, 120-180 rpm, avoid light, obtain secondary processing indigo blue.The application first utilizes trichoderma to carry out biological transformation to indigo blue, can significantly improve the content of its key anti-tumor component indigo carmine with specificity, and the increase is more than 150%.In vitro anti-tumor experiment shows that the inhibitory activity of secondary processing indigo blue prepared by the application to human leukemia K562 cells and human colon adenocarcinoma cell SW480 cell is significantly better than ordinary indigo blue.The product of the application can be used for preparing medicine for preventing and / or treating leukemia, colon adenocarcinoma, process controllable, suitable for industrialized production, and provides a new way for developing efficient indigo blue anticancer new drug.

The invention discloses a pharmaceutical composition for inducing leukemia cell copper death and application thereof, and relates to the technical field of tumor cell apoptosis. The active ingredients of the pharmaceutical composition are oleanolic acid and illlisemom. It is found for the first time that oleanolic acid can significantly up-regulate expression of a copper death key regulatory factor FDX1, when oleanolic acid is used in combination with a copper ion carrier Ilismor, a large synergistic effect can be generated through an FDX1 / DLAT axis, leukemia cells are significantly induced to generate copper death, and therefore in-vitro proliferation and in-vivo tumor forming ability of the leukemia cells are effectively inhibited. The composition provides a new drug development strategy with a clear mechanism for treatment of leukemia, especially drug-resistant leukemia.

The invention relates to the technical field of medicines, in particular to an enantiomer-atesane type diterpenoid compound as well as a preparation method and an application of the enantiomer-atesane type diterpenoid compound. The enantiomer-atesane diterpenoid compound disclosed by the invention is derived from plants, has anti-tumor activity, has cytotoxicity to human leukemia cells, human liver cancer cells and human cervical cancer cells, and is relatively good in inhibitory activity. Wherein the compound 3 has the best effect, the IC50 values of the compound 3 to three human tumor cells are 7.5 + / -1.2 micromole per liter, 9.8 + / -1.0 micromole per liter and 10.1 + / -0.9 micromole per liter respectively, and the activity of the compound 3 is equivalent to that of a positive control drug mitomycin. Particularly, the compound 3 also has good cytotoxicity to drug-resistant liver cancer cells (Huh7-LR cells), and the IC50 value of the compound 3 is 9.6 + / -1.1 micromole per liter. The compound 3 shows huge potential as a lead compound by virtue of the novel chemical structure and potent cytotoxicity shown in various cell lines.

The present invention relates to a specimen analyzer and a specimen analysis method, which make it possible to screen CML patients in the early stage of onset, which are difficult to implement in a blood cell counting test. A specimen analyzer includes: a measurement unit that acquires optical information of cells by irradiating a plurality of diffracted lights generated by light incident on a diffractive optical element to the cells contained in a specimen; and an analysis unit that analyzes the optical information obtained by the measurement unit by means of an artificial intelligence algorithm, thereby acquiring information on leukemia cells contained in the specimen.

The application discloses a DNA nanocage probe for leukemia cell multi-specific membrane protein logic circuit analysis, a kit and a method thereof, and realizes in-situ imaging analysis on three target membrane proteins by using a probe of a cross-section octahedral DNA nanocage main frame, stable structure, and designing a three-specific recognition biological computing DNA molecule logic gate based on a nucleic acid aptamer (Sgc4f, TC01, Sgc8c), which provides a new tool and idea for early diagnosis of tumors and biomedical application of the DNA molecule logic gate in a complex cell system.

The invention discloses an enzyme response magnetic resonance imaging nanoprobe as well as a preparation method and application thereof. The enzyme response magnetic resonance imaging nanoprobe comprises a metal nanoparticle with a surface functional group A as an imaging basic unit, and a polypeptide sequence with functional groups B at two ends as a cross-linking agent and an enzyme response unit, the enzyme response magnetic resonance imaging nano-probe is a metal nano-particle cross-linked body formed by cross-linking the metal nano-particles through a polypeptide sequence. The enzyme response magnetic resonance imaging nanoprobe disclosed by the invention can be specifically cut by a high-expression enzyme in a cell differentiation process to form monodispersed metal nanoparticles, so that signal transformation is presented on magnetic resonance imaging; meanwhile, the enzyme response magnetic resonance imaging nanoprobe can establish effective association among the probe existence form, the cell state and the imaging signal, and is used for tracking the directional differentiation process of mesenchymal stem cells, neural stem cells and promyelocytic leukemia cells in real time.

The application discloses an enzyme-responsive magnetic resonance imaging nano probe and a preparation method and application thereof. The enzyme-responsive magnetic resonance imaging nano probe comprises a surface functional group A metal nanoparticle as an imaging basic unit, and a functional group B polypeptide sequence as a crosslinking agent and an enzyme-responsive unit; and the enzyme-responsive magnetic resonance imaging nano probe is a metal nanoparticle crosslinking body formed by crosslinking the metal nanoparticle through the polypeptide sequence. The enzyme-responsive magnetic resonance imaging nano probe can be specifically cut by an enzyme highly expressed in a cell differentiation process, and forms a monodispersed metal nanoparticle, so that a signal change is presented on magnetic resonance imaging. Meanwhile, the enzyme-responsive magnetic resonance imaging nano probe can establish an effective correlation among a probe existing form, a cell state and an imaging signal, and is used for real-time tracking of a directional differentiation process of mesenchymal stem cells, neural stem cells and promyelocytic leukemia cells.

This invention provides a method for preparing a non-natural humanized chimeric anti-human CD45RA antigen receptor, which specifically binds to the human CD45RA antigen by expressing CAR protein on T cells. Based on a humanized 3A4 antibody, this invention constructs a lentiviral expression vector pLenti / Hu3A4-4-1BB-3ζ. Compared with murine CAR, the humanized CAR significantly reduces immunogenicity, noticeably decreases the production of anti-scFv antibodies, and avoids the HAMA reaction. Research results show that Hu3A4CAR-T cells can specifically bind to the CD45RA-highly expressing myeloid leukemia cell line KG1a. Hu3A4CAR-T cells can target and kill 3A4-positive cell lines and leukemia cells, alleviate the human anti-mouse antibody response, and significantly reduce the production of anti-scFv antibodies, thereby ensuring the CAR's killing activity.

The invention provides a use of a marker or a combination thereof in preparation of a product for prediction, diagnosis or auxiliary diagnosis of measurable residual diseases, the measurable residual diseases occur after clinical complete remission of acute myelogenous leukemia patients, and the marker or the combination thereof comprises a C-X-C chemokine receptor 4 gene. According to the method, a multi-parameter flow sorting technology is adopted, leukemia cell populations are separated from bone marrow samples of patients in the first diagnosis stage and the AML MRD stage, and a sufficient number of residual disease cells are successfully captured through a single cell transcriptome sequencing technology. The CXCR4 low-expression cell is identified to be capable of being used as a common marker of an MRD cell, and is verified in a clinical AML patient specimen. And an innovative scheme is provided for MRD monitoring of AML patients lacking clear molecular markers. And meanwhile, a CXCR4 low-expression cell is provided as a function substitution model of the MRD cell, so that the technical limitation of insufficient residual cells in the traditional research is broken through, and a reliable research system is established for systematically exploring the biological characteristics of the MRD cell.

This invention relates to the application of PWWP2B as a target in the preparation of drugs for the treatment of leukemia, belonging to the field of biomedical technology. To address the problem that traditional AML treatment targets lack tumor specificity and fail to meet clinical needs, this invention provides the application of PWWP2B as a target in the preparation of drugs for the treatment of leukemia. This invention demonstrates that PWWP2B is highly expressed in acute myeloid leukemia (AML) cells, and as a molecular marker, it can accurately distinguish AML from healthy individuals or non-leukemia patients. In vivo and in vitro experiments demonstrate that knocking out PWWP2B can significantly inhibit the proliferation and colony formation of AML cells, promote their differentiation and apoptosis, and inhibit the activity of leukemia cells in patients. This invention also reveals for the first time a novel use of the small molecule compound EZM0414 in the treatment of AML and its synergistic effect when used in combination with methyltransferase inhibitors.

OF THE INVENTION USE OF INHIBITORS OF THE N-ACETYLASPARTATE SYNTHETASE FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIAS Acute Myeloid Leukemias (AML) are characterized by the proliferation of immature blood cells, leading to suppression of normal hematopoiesis. Despite existing treatments, resistance and relapse are common. A metabolomic analysis revealed increased N-Acetyl-Aspartate (NAA) levels in leukemic cells compared to normal HSCs, with high NAA levels linked to poor prognosis. The inventors studied the gene NAT8L, responsible for NAA synthesis, and found correlations with patient survival. Using CRISPR-cas9, the inventors targeted NAT8L in AML cell lines and observed that NAA depletion improved response to treatments and increased survival in vivo. Inhibiting NAA synthetase thus represents a therapeutic strategy to enhance chemotherapy efficacy and prevent relapse in AML patients.

The present application relates to the application of TRMT61A as a target point in the preparation of AML treatment drugs, and belongs to the technical field of biological medicine. In order to solve the problem of the clinical applicability limitation of current chemotherapy and targeted inhibitor treatment in AML treatment, the present application provides the application of TRMT61A as a target point in the preparation of AML treatment drugs, wherein the drug comprises a TRMT61A inhibitor Thiram or a targeted sgRNA. Knocking out TRMT61A can significantly inhibit AML cell proliferation, promote apoptosis differentiation and block the cell cycle. Thiram has an inhibitory effect on AML cell growth and patient-derived leukemia cell viability, and shows a synergistic anti-leukemia effect when combined with Rapamycin, ORY-1001 or the clinical chemotherapy drug Ara-C, can significantly inhibit leukemia cell infiltration in a mouse model and prolong the survival period. The present application provides a new strategy for AML treatment.

The application discloses application of AZ505 combined with Imatinib in preparation of a drug composition for treating leukemia, and belongs to the technical field of biotechnology. Experiments prove that the combined use of AZ505 and Imatinib can induce apoptosis of leukemia cells, and meanwhile, can inhibit the activity of leukemia cells.

The invention discloses an application of lupeol as an FLI1 protein inhibitor in preparation of an anti-erythroleukemia drug, and belongs to the technical field of biological medicines, and the lupeol plays an anti-erythroleukemia role by inhibiting erythroleukemia cell proliferation and / or inducing erythroleukemia cell apoptosis. The lupeol is directly combined with the FLI1 protein and reduces the expression level of the FLI1 protein to realize the FLI1 protein inhibition effect. The invention reveals and verifies that the natural compound lupeol can inhibit the expression and function of the FLI1 protein by directly targeting and combining with the FLI1 protein for the first time, thereby playing a role in resisting erythroleukemia. A brand-new FLI1 protein inhibition-based action mechanism is provided for the treatment of erythroleukemia, and the limitation that the existing treatment means mainly depends on traditional cytotoxic drugs is broken through.

The application provides a fluorescent probe for myeloperoxidase detection, and a preparation method and application thereof. The fluorescent probe can detect MPO in living cells, greatly shortens the detection time, has low production cost, high specificity, and can be fixed on the protein of the cell after response, thereby avoiding non-specific fluorescent signal transmission and reducing false positives in the detection process. Meanwhile, the fluorescent probe can realize the function of distinguishing myeloid leukemia cells from lymphoid leukemia cells.

This invention discloses a tetracyclic analogue-sulfonamide hybrid of *Zanthoxylum bungeanum* alkaloids, possessing the following general formula. The invention also provides a method for preparing the tetracyclic analogue-sulfonamide hybrid of *Zanthoxylum bungeanum* alkaloids, comprising dissolving compound 10 or compound 11 and triethylamine in dichloromethane, adding benzenesulfonyl chloride derivative 12a-12e at low temperature, stirring, and then stirring at room temperature until the starting material spot disappears. The reaction is monitored by TLC. After the reaction is complete, the product 13a-13e or 14a-14e is obtained by column chromatography separation and purification. The tetracyclic analogue-sulfonamide hybrid of *Zanthoxylum bungeanum* alkaloids provided by this invention has been shown in in vitro antitumor experiments to exhibit strong inhibitory effects on human cervical cancer cells in leukemia cells, human liver cancer cells, human lung cancer cells, human cervical cancer cells, and normal human liver cells.

Methods for treating leukemia are disclosed based on detecting specific cell states and transcriptional programs within leukemic cells. This disclosure presents a novel therapeutic method for treating acute lymphoblastic leukemia (ALL), including BCR-ABL positive and BCR-ABL1-like ALL subtypes. The method involves detecting specific cell states and transcriptional programs in patient samples and administering targeted therapies based on these characteristics. For a pre-B cell-like state or pre-BCR signaling program, a combination of tyrosine kinase inhibitor (TKI) and SYK inhibitor is used. Conversely, a progenitor-like state or stress-autophagy program is treated with a TKI and a p38 MAPK inhibitor. This approach aims to improve treatment efficacy by tailoring therapy to the leukemia's unique molecular and cellular features, particularly in relapsed cases or when minimal residual disease is present.

The application relates to application of BAHD1 as a target point in preparation of a leukemia treatment drug and belongs to the technical field of biological medicine. In order to solve the problems of high drug resistance and high recurrence of an acute leukemia treatment scheme, the application provides application of BAHD1 as a target point in preparation of a leukemia treatment drug. It is proved that BAHD1 is highly expressed in acute leukemia cells, and is used as a molecular marker for diagnosis of acute leukemia. It is proved that knocking out BAHD1 can significantly inhibit proliferation and self-renewal of the acute leukemia cells, promote apoptosis and differentiation of the acute leukemia cells, effectively inhibit proliferation of leukemia cells in the body, reduce tumor load and extramedullary infiltration, and significantly prolong the survival period. In addition, knocking out BAHD1 can significantly enhance the sensitivity of the acute leukemia cells to traditional chemotherapy drugs and targeted treatment drugs.

The present application relates to the use of DDX39B protein inhibitor for preparing a therapeutic drug for acute leukemia, and belongs to the technical field of biological medicine. In order to solve the problem that the current treatment scheme for acute leukemia is single and new drugs are scarce, the present application provides the use of DDX39B protein inhibitor for preparing a therapeutic drug for acute leukemia. The present application discloses that targeted inhibition of DDX39B can significantly hinder the proliferation of leukemia cells, promote cell apoptosis and differentiation, block cell cycle progression, and delay disease progression and prolong the survival of model animals in vivo. Based on the RNA binding pocket structure of DDX39B, through high-throughput drug screening, the present application first identifies a small molecule compound HMU-4051C as a DDX39B targeted inhibitor that effectively kills leukemia cells, and develops a new use of DDX39B protein inhibitor in preparing a therapeutic drug for acute leukemia.

The invention relates to an aporphine-benzylisoquinoline alkaloid dimer as well as a preparation method and application thereof, and belongs to the field of natural medicines and biological medicines. The aporphine-benzylisoquinoline alkaloid dimer has a structural general formula shown in the specification, in the formula, R1, R2, R3, R4, R5, R6, R7 and R8 are independently selected from hydrogen, methoxyl, hydroxyl or two adjacent substituent groups are methylenedioxy, so that a five-membered ring is formed; and R9 is selected from hydrogen, methoxyl or hydroxyl. Six novel aporphine-benzylisoquinoline alkaloid dimers are extracted and separated from roots of thalictrum omeiensis, and through detection, the aporphine-benzylisoquinoline alkaloid dimers have obvious growth inhibition effects on human acute promyelocytic leukemia cells HL-60 and human prostate cancer cells PC-3, and have the prospect of preparing medicines for preventing and treating tumors.

This invention discloses an enzyme-sensitive PDC-type PROTAC modified with a human leukemia cell-targeting transmembrane peptide, its preparation method, and its applications, belonging to the field of tumor targeted therapy technology. This PDC-type PROTAC is composed of a hypoxia-inducible factor 1α (HIF-1α) protein fragment linked to imatinib via dodecanoic acid, and further modified with the human leukemia cell-targeting transmembrane peptide Cyclo-C9C-R and the cathepsin B-sensitive sequence GFLG. The modified PDC-type PROTAC can release the original drug under the catalysis of cathepsin B, with minimal impact on THP1 cell viability, but effectively inhibits the proliferation of K562 and KU812 cells, degrades target proteins, induces apoptosis, and affects the cell cycle. This gives the PDC-type PROTAC significant advantages in the preparation of anti-tumor drugs, particularly showing promising application prospects in the development of drugs targeting human chronic myeloid leukemia cells and human peripheral blood basophilic leukemia cells, opening up a new field for PROTAC drug development.

Disclosed is use of a tetrahydroisoquinoline compound in the preparation of an anti-leukemia drug. The tetrahydroisoquinoline compound has a significant inhibitory effect on leukemia cells and low toxicity to organisms. This compound expands the range of drugs for clinical treatment of leukemia, and is suitable for mass production.

The application provides a use of vincristine and lithium carbonate as co-active ingredients in the preparation of a medicament for treating tumors. The vincristine and lithium carbonate as co-active ingredients of the application have a killing effect on various leukemia cells, including human acute lymphoblastic leukemia cell lines, chronic myeloid leukemia cells, acute monocytic leukemia cell lines; in particular, for human acute lymphoblastic leukemia cell lines, compared with single free drugs (lithium carbonate or vincristine), lithium carbonate and vincristine free drug combination, the leukemia cell proliferation can be more effectively inhibited; in addition, the vincristine and lithium carbonate as co-active ingredients of the application can obviously stimulate the generation of granulocyte colony-stimulating factor, and alleviate the neutropenia side effect caused by chemotherapy.

The application relates to the field of biological medicine, in particular to application of lysosome ion channel CLN7 as a target in preparation of a drug for treating myeloid leukemia. In K562 and other myeloid leukemia cell strains, the proliferation ability of leukemia cells is significantly inhibited after CLN7 expression is knocked down by using specific shRNA interference technology, and cell apoptosis is greatly promoted. Experiments prove that inhibition of CLN7 enhances lysosome degradation function, promotes degradation of leukemia-related pathogenic proteins, and blocks survival signal dependence of leukemia cells. Preliminary results show that the influence of inhibition of CLN7 on normal hematopoietic cells is significantly lower than that on leukemia cells, which indicates that the treatment window is good.

The invention provides an anti-leukemia small molecule compound TIP-20 targeting FLT3 and application of the anti-leukemia small molecule compound TIP-20, and belongs to the technical field of biological medicine. The invention develops a novel FLT3 kinase inhibitor TIP-20, which can enhance the antigen presentation effect of FLT3-ITD leukemia cells, can be combined with FLT3 protein, stabilizes the structure of FLT3, and further inhibits FLT3 phosphorylation and downstream pathway activation. The TIP-20 has an obvious inhibiting effect on the growth of leukemia cell strains, and can inhibit the growth of leukemia cells with FLT3 mutation by inhibiting phosphorylation of FLT3, promoting cell apoptosis and cycle arrest. Moreover, FLT3 wild type cells have good tolerance to TIP-20, have a wide therapeutic window with FLT3-ITD mutated acute myelogenous leukemia cells, and are expected to bring a better choice for treatment of FLT3 mutated AML patients.

The invention discloses application of ziyuglycoside II in preparation of a medicine for treating and relieving acute promyelocytic leukemia and / or ATRA-resistant acute promyelocytic leukemia and a medicine composition, and belongs to the technical field of medicine. Experiments prove that ziyuglycoside II can inhibit proliferation of acute promyelocytic leukemia cells (NB4) and transretinoic acid (ATRA) drug-resistant acute promyelocytic leukemia cells (NB4-R2), induce differentiation of the NB4 and the NB4-R2, promote apoptosis of the NB4-R2 cells and relieve disease development of ATRA drug-resistant cell xenotransplantation acute promyelocytic leukemia. The ziyuglycoside II is developed as a novel drug for resisting acute promyelocytic leukemia or an auxiliary component thereof, and the ziyuglycoside II has obvious effects of resisting acute promyelocytic leukemia and drug-resistant acute promyelocytic leukemia; the invention provides a new approach and means for treating acute promyelocytic leukemia and drug-resistant acute promyelocytic leukemia.

The present application relates to the technical field of organic synthesis, and particularly provides an indole compound, a preparation method and application thereof. The chemical structural formula of the indole compound is shown as formula I. The provided indole compound can inhibit the growth of Jurkat leukemia cells in combination with dexamethasone at different concentrations, and the indole compound in combination with dexamethasone can activate the phosphorylation level of glucocorticoid, inhibit the PI3K / AKT and JAK2 / STAT3 signal pathways related to glucocorticoid resistance to overcome the drug resistance of glucocorticoid, and make the leukemia cells die.

The invention discloses a bispecific bionic nanomaterial and a preparation method and application thereof, and belongs to the field of biological medicine.The bispecific bionic nanomaterial is composed of a marrow stromal cell membrane modified enzyme-loaded porphyrin covalent organic framework, an anti-CD3 antibody and an anti-PD-L1 antibody, the enzyme-loaded porphyrinyl covalent organic framework is loaded with glucose oxidase, and the antibody is anchored on a phospholipid bilayer of the enzyme-loaded porphyrinyl covalent organic framework modified by a cell membrane through a physical effect; the bispecific bionic nano material prepared by the invention can block a CXCR4 / CXCL12 axis and inhibit migration and adhesion of leukemia cells; according to the bispecific bionic nanomaterial, hydrogen peroxide generated by decomposition of glucose is converted into hydroxyl radicals for chemical kinetic treatment by utilizing peroxidase-like activity of a porphyrin-based covalent organic framework, and T cells are redirected to leukemia cells to play a killing role.