Recent Advance of Newly Therapy for Chronic Myeloid Leukemia with BCR-ABLT315I Mutation--Review / 中国实验血液学杂志

BCR-ABLT315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABLT315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.

Research Advances on the Biological Characteristics of Hematological Malignant Cells Immunologically Regulated by Exosome--Review / 中国实验血液学杂志

Abstract　　The minimal residual disease (MRD) is the origin element that caused the relapse and drug resistance of hematological malignancies, the immune cells play a great role to clear MRD. A variety of immune cells have anti-tumor effects. However, tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment. Many different cell types, including immune cells, mesenchymal cells and tumor cells in tumor microenvironment release exosomes. The latest researches indicate that "cargo" and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell (migration, activation, proliferation, secretion and NKG2D expression), macrophage (migration and secretion) and dendritic cell (maturation and presentation), but also regulate the expression of PD-L1 and CCR2, CCL2 secretion and transformation of monocytes. The altered function of immune cells will eventually have effect on the progression of hematological malignancies.

MSC Senescence-related Signaling Pathway - Review / 中国实验血液学杂志

The replicative senescence of mesenchymal stem cells(MSC) during the in vitro expansion limits their use in the research and treatment of many disease. Also, MSC senescence may promote the individual senility, hypofunction of tissue and organ, and tumorigenesis. Thus, in order to better understand the senescent mechanism and delay the senescence, even reverse MSC senescence, the roles of signaling pathway, such as Wnt/β-catenin, MAPK/ERK, PI3K/AKT and ROS-related signaling pathway during the MSC senescence all were reviewed, so as to can deepen the under-standing of MSC senescence and provide a new thinkings for delaying, even reversing the MSC senescence.

Role of Exosomal miRNA in Multiple Myeloma Progression and Its Possible Mechanism -Review / 中国实验血液学杂志

Multiple myeloma (MM)is a kind of plasma tumor originated from B cell line. Its incidence ranks in second place of hematopoietic malignancies. Although continued progress was made in treatment of MM,the survival rate and prognosis of MM patients are still not satisfactory. Further understanding of the pathogenesis of MM may provide information to develop new treatment strategies, so as to improve survival rate and ameliorate its prognosis. Many researches have demonstrated that bone marrow microenvironment plays an important role in MM pathogenesis, which regulates the biological properties of MM cells, including migration and proliferation, through miRNA, mRNA and protein contained in the exosomes released from the cells in the tumor microenvironment. Recently, as the tumor suppressor genes and oncogenes, exosomal microRNA become a hot spot in research. Compared with those of the normal ones, exosomes in MM have less miR-15a and/or more miR-135b and miR-21. These differences will accelerate the progression of MM via PI3K/Akt/eNOS/VEGF pathway, FIH-HIF pathway, MAPK/ERK/Ras pathway and so on, that are expected to become the new targets for the treatment of MM. This review summarizes the role and the possible mechanism of exosomes in the progression of MM.

Role of Exosomes in the Cross-Talk between Leukemia Cells and Mesenchymal Stem Cells -Review / 中国实验血液学杂志

More and more studies have demonstrated that bone marrow microenvironment, the fundament of the multiplication and differentiation of hematopoietic stem cells, plays a crucial role in leukemia progression and resistance to treatment. It provides a permissive environment for minimal residual disease and contributes to relapse and multidrug resistance. Mesenchymal stem cells are a kind of important stromal cells in bone marrow niche. In recent researches, MSC have been shown to be one of the major factors modulating the biological features of leukemia cells. The cross-talk between MSC and leukemia cells can take place not only by direct contact, but also by exosome exchange. Exosomes are nano-sized vesicles released by a variety of cells, which contain protein, RNA and mRNA. They are effective tools for transportation between cells, and play an important role in many physiological and pathological processes. Exosome is a new topic in the research of leukemia and microenvironment. The exosome research will help elucidate the mechanism of leukemia, thus providing new ideas for the treatment.