Construction method and application of primary MM (multiple myeloma) mouse model

Abstract

The invention discloses a construction method and an application of a primary MM (multiple myeloma) mouse model. The method comprises steps as follows: high-frequency mutated proto-oncogenes are screened from sequencing results of MM patient samples and taken as driver genes, and a retroviral vector is constructed, infects IgM positive B cells of a mouse in vitro and performs induced transformation into an MM model in the body of the mouse; proto-oncogene combinations of ten patients are screened out, and cMYC and KRAS12V are determined to be the best. The model is applied to research of humanMM pathogenesis, chemical drug screening of MM, improvement of existing therapeutic schedules, evaluation of new drug or targeted drug combination and evaluation of the model for cellular immunotherapy and antibody therapy. The constructed primary MM model has great significance for scientific research of molecular mechanism of MM genesis and development and exploration of new MM treatment targets. The animal module is fast to form and realizes 100% tumor formation, and a theoretical basis and an evaluation system are provided for development of new target identification and new treatment method evaluation of MM on the basis of biotherapy.

Description

technical field [0001] The invention relates to the technical field of multiple myeloma research, in particular to a method for constructing a primary multiple myeloma mouse model and its application. Background technique [0002] Multiple myeloma (Multiple Myeloma, MM) is a malignant plasma cell disease, and its tumor cells originate from plasma cells in the bone marrow, and plasma cells are cells in the terminal stage of B lymphocyte development. In China, its incidence rate is estimated to be 2-3 / 100,000, with a male to female ratio of 1.6:1, and most patients are >50 years old. Currently, WHO classifies it as a type of B-cell lymphoma called plasma cell myeloma / plasma cell tumor. It is characterized by abnormal proliferation of bone marrow plasma cells with overproduction of monoclonal immunoglobulin or light chain (M protein), and very few patients can be non-secretory MM that does not produce M protein. Multiple myeloma is often accompanied by multiple osteolytic ...

AI Technical Summary

Problems solved by technology

However, the shortcomings of transgenic mice, such as high cost, time-consuming, uneven tumor formation rate, and inability to fully simulate the development of human MM, limit their use and value.

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