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Application of luteinizing hormone in inhibition of development of myeloid leukemia

A technology of luteinizing hormone and myeloid leukemia, applied in the field of biomedicine, can solve the problem that tumor cells cannot be completely eliminated

Active Publication Date: 2019-11-01
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the existence of multiple drug resistance mechanisms of cancer cells in AML, single drug therapy often cannot completely eliminate tumor cells. Therefore, AML treatment needs to be combined with multiple drug regimens for specific situations at the same time. Finding more efficient targets for the treatment of AML has become the current acute One of the central issues in myeloid leukemia research

Method used

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  • Application of luteinizing hormone in inhibition of development of myeloid leukemia
  • Application of luteinizing hormone in inhibition of development of myeloid leukemia
  • Application of luteinizing hormone in inhibition of development of myeloid leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0123] Example 1: In the blood system, Lhcgr expression is restricted to HSCs and MPPs

[0124] Luteinizing hormone (LH) is associated with the onset of puberty and plays an important role in gonadogenesis in both male and female mice. Previous studies have found that Lhcgr is mainly expressed in primitive hematopoietic stem cells (HSCs) and multipotent progenitor cells MPPs ( figure 1 , A). In mice of different sexes, there was no heterogeneity in the expression of Lhcgr in HSCs ( figure 1 , B). The expression of Lhcgr presents temporal changes in different developmental stages of mice. During the fetal liver period, the expression of Lhcgr in the mouse bone marrow is maintained at the background level. After birth, the expression level of Lhcgr in the mouse bone marrow gradually increases until after birth. 8 weeks to reach a stable ( figure 1 , C), these evidences show that hematopoietic stem cells in the bone marrow are direct targets of LH signaling.

[0125] Simulta...

Embodiment 2

[0126] Example 2: Under steady state conditions, Lhcgr knockout promotes HSC self-renewal and hematopoiesis in mouse bone marrow

[0127] The present inventor constructed Lhcgr gene knockout mice and detected and analyzed hematopoietic-related phenotypes after adulthood, and found that at 8 weeks of age, Lhcgr - / - In the mice, the total number of cells in the bone marrow and the frequency of HSCs were significantly higher than those of the littermate control mice, and the number of HSCs also increased significantly ( figure 2 , A), the number of downstream MPPs, B cells, and T cells increased significantly compared with the control group ( figure 2 , B-F). Competitive hematopoietic lineage reconstitution experiments revealed that the same amount of Lhcgr - / - Mouse bone marrow hematopoietic cells have stronger hematopoietic lineage remodeling ability ( figure 2 , G). Taken together, these data suggest that LH signaling plays an important regulatory role in HSC self-renew...

Embodiment 3

[0128] Example 3: Lhcgr knockout leads to accelerated expansion of leukemia cells

[0129] In this example, the inventors constructed a mouse model of acute myeloid leukemia driven by the MLL-AF9 proto-oncogene. Lhcgr - / - Mice and control Lhcgr + / + Mouse bone marrow C-kit positive cells were sorted by flow cytometry, infected with MLL-AF9 retrovirus, and then transplanted into irradiated recipient mice by ocular vein injection. Using flow cytometry analysis technology, the proportion of YFP-positive cells in the peripheral blood of recipient mice was detected four weeks after transplantation, and the results showed that YFP in the peripheral blood of recipient mice in the experimental group + Lhcgr - / - The proportion of donor leukemia cells (32.5%) was significantly higher than that of the control group (11.7%) ( image 3 , A-B). This AML mouse model mainly expresses the surface molecular markers Mac-1 and Gr-1 of myeloid cells, while the expression of molecular markers r...

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Abstract

The invention provides an application of a luteinizing hormone in inhibition of development of myeloid leukemia, and particularly provides an application of a luteinizing hormone or a receptor accelerant thereof in preparation of a preparation or a composition, and the preparation or the composition is used for inhibiting myeloid leukemia. The invention also provides a diagnostic kit for diagnosing and treating myeloid leukemia and a method for screening or determining a potential therapeutic agent for treating myeloid leukemia.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of targeting luteinizing hormone and its receptor in inhibiting the development of myeloid leukemia. [0002] Background of the invention [0003] Acute myeloid leukemia (AML) is a cancer characterized by the infiltration of bone marrow, blood and other tissues by abnormally differentiated proliferative hematopoietic cells. As a blood disease that seriously threatens human life, the cure rate of acute myeloid leukemia in patients under the age of 60 is 35-40%, while in patients over the age of 60, the cure rate of the disease is only 5%. %-15%. Despite the many advances in the genetics and epigenetics of acute myeloid leukemia, the general strategy for the treatment of AML has not changed substantially in the past three decades. It was previously believed that the failure of AML treatment is mainly due to the generation of drug-resistant mutations in cells caused by dr...

Claims

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Application Information

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IPC IPC(8): A61K38/09A61K45/06A61P35/02A61K49/00G01N33/76G01N33/50
CPCA61K38/09A61K45/06A61P35/02A61K49/0008G01N33/5008G01N33/76G01N33/5011G01N2333/59A61K2300/00
Inventor 周波彭义
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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