7 results about "DLK1" patented technology

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.

This invention relates to the diagnosis and evaluation of juvenile myelomonocytic leukemia (JMML). In particular, the invention relates to a method for diagnosing JMML in a subject, comprising: a) at least one biomarker present on or in hematopoietic stem cells and progenitor cells (HSPCs) in a biological sample, i) CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RAB11A, SELL, VAMP5, FCMR, CLEC7A, NDFIP The present invention relates to a method comprising the steps of: 1) determining the amount of at least one biomarker selected from each of the following groups: 1) Group I consisting of CLEC9A, HCST, LPAR6, HLA-DQA1, HLA-DRB5, and CD34; and 2) Group II consisting of IGLL1, BEST1, EREG, SLC5A3, SERK, PRRG3, NINJ1, MGST1, and HLA-G; b) comparing the determined amount in step a) with a reference; and c) diagnosing JMML based on the comparison in step b). Furthermore, the present invention relates to a method for classifying subjects suffering from JMML into a low- or high-risk JMML group. Furthermore, the present invention relates to the use of at least one biomarker present on or in HSPC in a biological sample for diagnosing JMML to a low- or high-risk JMML group in subjects who have JMML or are at risk of developing it. Furthermore, the present invention relates to a kit for diagnosing JMML in a subject or for classifying a subject suffering from JMML into a low- or high-risk JMML group.Furthermore, the present invention relates to an inhibitor for use in the treatment and / or prevention of JMML that specifically inhibits at least one biomarker selected from the group consisting of CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RAB11A, SELL, VAMP5, FCMR, CLEC7A, NDFIP1, CLEC9A, HCST, LPAR6, HLA-DQA1, HLA-DRB5, CD34, IGLL1, BEST1, EREG, SLC5A3, SELK, PRRG3, NINJ1, MGST1, and HLA-G, which are present on or in hematopoietic stem cells and progenitor cells (HSPCs). The present invention further relates to a pharmaceutical composition for use in the treatment and / or prevention of JMML, comprising at least two inhibitors according to the present invention. Finally, the present invention envisions a method for treating and / or preventing JMML.

The invention discloses an early pregnancy loss diagnosis marker and application thereof. The marker provided by the invention comprises at least one of DLK1, SPTB, COL21A1 and SAR1A. The invention finds that DLK1, SPTB or COL21A1 and SAR1A can be respectively used as a molecular marker and a target of a complete grape tire, a partial grape tire and spontaneous abortion in an early pregnancy loss subtype, and a clinical sample is detected and further verified by a western blot method and an immunohistochemical method. The method can be used for guiding rapid diagnosis of early pregnancy loss, and has important practical application value.

Activating mutations in CTNNB1 gene encoding β-catenin is encountered in approximately 30% of hepatocellular carcinoma (HCC) and in more than 80% of hepatoblastoma. In ApcΔhep model, the inventors unravel the biggest cluster of non-coding RNAs identified called the DLK1 / DIO3 locus as the most significantly induced region in response to β-catenin activation regarding transcription of coding and non-coding elements. Using in vivo Crispr / cas9 strategy, the inventors were able to demonstrate that β-catenin and its cofactor TCF-4 directly bind on a WRE-containing site located upstream of Meg3 to create an active enhancer regulatory region engaged in chromatin remodeling in the direct vicinity of this binding site but also at distance by long range DNA-DNA contacts to promote transcription of the entire locus. These Crispr / cas9 constructs have also proved to be a valuable strategy to impair the locus expression in the murine models mimicking HCC and hepatoblastoma (ApcΔhep and β-cateninΔExon3 tumors) but also in two cell lines with activating mutations in β-catenin encoding gene, the murine Hepa1-6 and human HuH6 cells. In transformed cells, it significantly impaired cell proliferation in vitro and HuH6 sternness capacities but also tumor progression in Hepa1-6 allografts. In mouse models, the locus editing during early steps of tumorigenesis decreased the proliferation of ApcΔhep preneoplastic hepatocytes but also those of ApcΔhep and β-cateninΔExon3 tumor cell resulting in impairment of tumor size. In conclusion, the results demonstrate that disrupting the β-catenin / TCF-4 binding site located upstream of Meg3 in the DLK1 / DIO3 locus represents a very interesting approach for the treatment of liver cancers.

The present invention relates to the diagnosis and assessment of juvenile granulocytic leukemia (JMML). In particular, it relates to a method of diagnosing JMML in a subject, said method comprising: a) determining the amount of at least one biomarker present on or in hematopoietic stem and progenitor cells (HSPC) in a biological sample, said at least one biomarker being selected from the group consisting of i) Group I consisting of CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RABI1A, SELL, VAMPS, FCMR, CLEC7A, NDFIP1, CLEC9A, HCST, b) comparing the quantity determined in step a) with a reference; and c) diagnosing the JMML based on the comparison of step b). In addition, the invention also relates to a method for classifying subjects suffering from JMML as a low-risk or high-risk group of JMML. Furthermore, the invention relates to the use of at least one biomarker present on or in HSPC in a biological sample for diagnosing JMML in a subject suffering from or at risk of developing into JMML as a low-risk or high-risk group of JMML. Furthermore, the present invention relates to a kit for diagnosing JMML in a subject or classifying a subject suffering from JMML as a low-risk group or a high-risk group of JMML. Furthermore, the present invention relates to the use of an inhibitor for the treatment and / or prevention of JMML, said inhibitor specifically inhibiting at least one biomarker selected from the group consisting of CD52, RAMP1, LTB, LST1, JAML, IFITM3, CD7, CD69, CD164, CD74, TNF, TFPI, DLK1, CD82, IGHM, CALCRL, RALA, SLC2A5, HSPA5, HLA-DRA, RABI1A, SELL, VAMPS, FCMR, CLEC7A, NDFIP1, CLEC9A, HCST, LPAR6, HLA-DQA1, HLA-DRB5, CD34, IGLL1, B, present on or in hematopoietic The invention also relates to a pharmaceutical composition for the treatment and / or prevention of JMML, said pharmaceutical composition comprising at least two inhibitors according to the invention. Finally, the present invention envisages a method of treating and / or preventing JMML.

To provide an antibody-drug conjugate comprising an antibody binding to DLK1 or an antigen-binding fragment thereof, and a pharmaceutical composition comprising the same.SOLUTION: Provided is an antibody-drug conjugate, or a pharmaceutically acceptable salt or solvate thereof, comprising an antibody or an antigen-binding fragment thereof, specifically binding to DLK1 (Delta-like 1 homolog (Drosophila)), and comprising a heavy chain variable region and a light chain variable region having CDR1, CDR2, and CDR3 consisting of specific amino acid sequences.SELECTED DRAWING: Figure 1

The invention discloses a bispecific antibody DLK1 / CD3 for treating liver cancer. The bispecific antibody DLK1 / CD3 comprises an anti-human DLK1 monoclonal antibody and an anti-human CD3 monoclonal antibody. The sequence of the single-chain variable region of the DLK1 monoclonal antibody and the single-chain variable region of the CD3 monoclonal antibody is VL (DLK1)-VH (DLK1)-VH (CD3)-VL (CD3). The bispecific antibody can form immune synapses by targeting tumor cells and T cells, directly activate the T cells and enhance the killing ability of the T cells to liver cancer cells.