Multiple myeloma (MM) is a malignant disease of bone marrow plasma cells. Existing treatments, including conventional chemotherapy, hematopoietic stem cell transplantation, immunotherapy, and targeted therapy, among others, have prolonged the survival and improved the quality of life of myeloma patients, but still cannot cure the disease. In recent years, research on the cytogenetics of multiple myeloma has attempted to open up a new pathway for the treatment of multiple myeloma. 1. MM is a plasma cell tumor of post-germinal center B-cell origin Most B-cell tumors, including MM, originate from germinal center (GC) or post-germinal center B-cells. Post-germinal center B cells are capable of producing protoplasmic cells that have successfully completed somatic hypermutation and IgH rearrangement before migrating to the bone marrow (BM). Protoplasmic cells eventually differentiate into plasma cells by the action of stromal cells in the bone marrow. Although plasma cells can arise from either protoplasmic or posterior germinal center B cells, monoclonal gammopathies of unspecified significance of the non-IgM type (MGUS) and MM are both monoclonal diseases of posterior germinal center origin with a protoplasmic/plasma cell phenotype characteristic of multiple loci in the bone marrow. Both have an extremely low proliferation rate, usually less than 1%, but the proliferation rate of tumor cells is elevated at the terminal stage of MM. In clonal plasma cell tumors, there must be more than 109 cells before enough immunoglobulin (Ig) is produced to pass plasma electrophoresis and a monoclonal Ig “spike” (M-Ig) appears. more than 10%. The genetic or phenotypic markers that distinguish MGUS from MM tumor cells have not been identified, and it is not possible to predict when a particular MGUS will develop into MM. clinically, the distinction between MM and MGUS is often made on the basis of >10% tumor cells in the bone marrow. The MM is more aggressive, and human MM cell lines are often derived from extramedullary MM (plasma cell leukemia). 2. Hypothesis of molecular pathogenesis of multiple myeloma In 40-60% of MM, primary chromosomal translocations or early secondary translocations lead to ectopic expression of oncogenes, directly (11q13 – cytokine D1 with 6p21 – cytokine D3) or indirectly (4p16, 16q23, others – cytokine D2) leading to cytokine D dysregulation. Whereas in other MM patients there is no primary translocation, dysregulation of cycyclin D1 (and sometimes possibly cycyclin D2) may be due to other mechanisms, such as abnormal interactions between bone marrow stromal cells. Dysregulation of one of the three cycyclin genes makes these clonal cells more sensitive to proliferative stimuli, leading to selective expansion of this clone in response to abnormalities in myeloid stromal cells capable of producing interleukin 6 (IL-6) and other cytokines. Abnormalities in chromosome number and structure are most often seen in trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, 21, monosomy of chromosome 13 or deletion of 13q14, often in MGUS and early MM. Whether these abnormalities occur before or after the primary IgH translocation remains unclear. However, monosomy of chromosome 13 (or deletion of 13q14) occurs in approximately 50% of MM, mostly with t(4;14) or t(14;16) translocations. The incidence of the 5 common translocations is very low in MM with the odd chromosome trisomy described above compared to non-hyperdiploid MM. Ectopic expression of cytokinin D1 but not IgH translocations is more common in the hyperdiploid TC2 group. It is not clear whether karyotypic instability exists in MM, but tumor progression is associated with secondary chromosomal translocations, such as c-myc. secondary translocations of Myc, which are less common in stable MM, are present in 50% of progressive MM and in almost all HMCL. therefore, myc gene dysregulation appears to be associated with disease progression to an aggressive, highly proliferative stage. k- or N-Ras [ or FGFR3 when there is a t(4;14) translocation] mutations are rare in MGUS, whereas the incidence of Ras mutations is 30-40% in early MM and more common in progressive MM with mutations in FGFR3. Mutations in p53 and single allele deletions occur later throughout the disease process. In the aggressive phase of MM, p16 gene methylation and pRb or p18 double allele deletion are often present. 3. The predictive value of karyotype abnormalities for prognosis and treatment response In addition to tumor load and secondary changes of MM such as anemia, bone disease, and immunodeficiency, the following indicators are factors for poor prognosis of MM: plasma cell marker index, abnormal chromosomal translocation, subdiploid karyotype, chromosome 13, monosomy of 13q, monosomy of chromosome 17, p53 deletion. Specific IgH translocations occurring in the late stages of the disease also suggest a poor prognosis. In particular, patients with tumors with t(4;14) translocations (TC4) have a significantly shorter survival with either standard or intensive therapy. Patients with tumors with t(14;16) translocations (TC5) had a poor, if not the worst, prognosis. In contrast, patients with tumors with t(11;14) translocations (TC1), who were treated with conventional chemotherapy, had a longer survival but were better treated with intensive therapy. Therefore, TC classification of MM with chromosomal translocations and cytokine D expression to classify MM into different subtypes is of clinical importance. 4. Novel therapeutic strategies for chromosomal translocations In the pathogenesis of MM, the cytokine D/RB pathway may become a target site for treatment. Histone deacetylase inhibitors (SAHA, depsipeptide) or DNA methyltransferase inhibitors (5`azido-2`deoxy-cytidine) can be used to reverse the methylation of the p16 gene. Recently, target site therapies for cytokinin D are also available, including regulation of mRNA translation, post-translational modifications, and enzyme function. The translation of cytokinin D mRNA is in tight modulation, and the translation of mRNA can be inhibited with desferrioxamine and eicosapentaenoic acid. Cytokinin D, along with many other cell cycle regulatory proteins, is activated post-translationally by proteasomal degradation, which may be another therapeutic target site. The proteasome inhibitor PS-341 has been used in phase III clinical trials in MM with good efficacy. Certain downstream kinases activated by cytokinin D may also be used as selective therapeutic targets. In addition, ectopic expression of cycyclin D1 is dependent on the interaction with bone marrow stromal cells. Application of response arrest and its derivatives targeting the interaction between tumor cells and the bone marrow microenvironment, inhibiting endothelial cell activity and anti-angiogenesis, has shown good clinical efficacy. FGFR3 (tyrosine kinase receptor) was expressed in patients with t(4;14). As a surface receptor, FGFR3 may be inhibited by monoclonal antibodies or selective tyrosine kinase inhibitors, becoming a therapeutic target site in MM with t(4;14). 5. Conclusion Research on the genetics of multiple myeloma is still in its infancy, and all multiple myeloma can not be clearly typed at present, and a more effective classification basis needs to be further explored. Different chromosomal translocations can be treated with different targets to obtain the best clinical efficacy and help us find more effective drugs for the treatment of multiple myeloma.