Multiple myeloma (MM) is a common malignant tumor of the hematologic system, which is a malignant clonal tumor of plasma cells characterized by plasma cell colonization and destruction of bone marrow. The monoclonal immunoglobulins or their light chain fragments (M component) secreted by a large number of abnormal proliferating plasma cells can cause a series of pathophysiological changes in the body, such as anemia, bone disease, hypercalcemia and renal insufficiency. The existing treatments including chemotherapy, radiotherapy and new drugs have significantly improved the efficacy of myeloma, but it is still incurable, suggesting that MM cells are biologically heterogeneous and a small proportion of cells are resistant to drugs as one of the reasons for tumor recurrence. The theory of tumor stem cells (cancer stem ce1ls, CSC) suggests that tumor stem cells are a small fraction of cells in tumor tissues with stem cell characteristics, which have high self-renewal ability and undirected differentiation potential and can drive tumor formation and growth, and may be the root cause of tumor generation, metastasis, recurrence and drug resistance. I. Multiple myeloma cells are heterogeneous Bergsagel et al. first confirmed the functional heterogeneity of MM cells in a mouse plasma cell tumor model, and confirmed that myeloma cells have the ability to form clones using the in vivo spleen colony formation assay, and then Park et al. performed in vitro clonal culture of myeloma cells extracted from mouse ascites, and 0.001-1% of the cells could form clonal colonies. Thus, the clonogenic ability of myeloma cells was confirmed in vitro. The same results were obtained in human MM, where the vast majority of MM cells were found to be in a quiescent state, while only 0.001-1% of primary MM specimens were able to form clones in vitro and were able to form clones again after isolation [4-6]. These results suggest that only a small fraction of cells have the ability to grow tumorigenically in vivo and clonally in vitro, and that multiple myeloma cells are heterogeneous, both in mouse plasma cell tumors and human plasma cell tumors. II. immunophenotype of multiple myeloma cells Normal plasma cells are terminally differentiated and express CD138, which is also expressed by plasma cells from all MM patients.Matsui et al [7] sorted samples from MM according to this surface marker and found that these CD138+/CD34- cells were unable to form clones in vitro; in contrast, CD138/CD34- cells were able to In contrast, CD138/CD34- cells were able to form mature clones in vitro, and these clones were able to expand, suggesting that CD138 cells have the ability to self-renew. These studies suggest that CD138 cells, but not 138+ cells, are clonogenic. The clonogenic myeloma cells highly expressed the B-cell surface antigens CD45, CDl9, CD20, and CD22, suggesting that the clonogenic capacity of myeloma is limited to the B-cell phenotype and that clonogenic myeloma CD138B cells are considered to be multiple myeloma stem cells. Further study of CD138 cells revealed that CD 19+CD 27+ memory B cells from peripheral blood of MM patients have the ability to grow clonally, and CD19+CD 27+CD138 cells have the ability to implant into NOD/SCID mice and differentiate into CD138+ mature MM plasma cells. Isolation of CD 19+CD 27+ cells from NOD/SCID mice and sequential transplantation also produced the same disease, suggesting that these cells have the properties of tumor stem cells and are capable of self-renewal and differentiation to produce the same disease as the primary tumor. III. Origin of MM stem cells Tumor stem cells may originate from normal cells or directed progenitor cells or their corresponding tissues, or even from other tissue cells. There are two hypotheses for the origin of MM stem cells: normal hematopoietic stem progenitor cells mutate to form MM stem cells. Mature MM cells dedifferentiate into MM stem cells. IV. Therapeutic impact of multiple myeloma stem cells MM tumor stem cells survive treatment, thus allowing disease recurrence. matsui et al [8] compared the sensitivity of MM plasma cells and tumor stem cells to dexamethasone, cyclophosphamide, lenalidomide and bortezomib and found that each drug was able to inhibit CD138+ plasma cells, whereas CD138MM tumor stem cells were relatively resistant to all these drugs. jana Jakubikova et al. reported that lenalidomide and thalidomide significantly reduced the proportion of SP cells by inhibiting the stimulatory effect of bone marrow mesenchymal cells. While normal stem cells are widely resistant to drugs, MM tumor stem cells share some of the same resistance mechanisms as normal stem cells. Some studies have found that normal stem cells are highly quiescent, and these properties can contribute to resistance to some cytotoxic drugs that require an active cell cycle or kill by targeted pathways. Assuming that standard therapeutic regimens do not significantly improve long-term survival times, several new therapeutic strategies targeting MM tumor stem cells have emerged, such as Cyclopamin as an inhibitor of the Hedgehog signaling pathway. Although current studies show that MM tumor stem cells are significantly different in immunophenotype and function from the plasma cells that make up the majority of tumor cells, and the clinical relevance of tumor stem cells is not yet clear, targeting tumor stem cells is an important direction for developing tumor treatment strategies, and the unique signaling pathways and biological markers of tumor stem cells can be used as therapeutic targets in combination with conventional chemotherapy and targeting tumor stem cells. The unique signaling pathways and biological markers of tumor stem cells can be used as therapeutic targets to combine traditional chemotherapy and targeting tumor stem cells in order to fundamentally cure the disease.