Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal blood circulation via body fluids. and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The conversation between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is INCB054329 Racemate usually believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, INCB054329 Racemate findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches. transcripts are detectable in CML cell-derived exosomes [79]. CML is usually a clonal myeloproliferative neoplasm caused by abnormal pluripotent hematopoietic stem cells transporting the BCR-ABL1 fusion caused by reciprocal translocation between chromosomes 9 and 22 and formation of the Philadelphia chromosome-positive (Ph+) CML [80]. In this case, conventional chemotherapy was not a curative treatment, and allogeneic HSCT remained the only possibility for a cure, although the number of cases who could undergo HSCT was limited. However, in the 2000s, tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 p210 protein dramatically changed the prognosis of CML patients. TKI is an innovative molecular targeted therapy that inhibits the progression of CML. Indeed, it has achieved major or deep molecular responses (DMRs) in about 80% to 90% of patients [81,82]. In order to accurately monitor the effects of treatment, a test that can measure MRD, a INCB054329 Racemate small amount of which remains in the patients body, is required, and the BCR-ABL1 mRNA test has become increasingly popular worldwide. In particular, this test has been established as an International Scale (Is usually) to promote the standardization of measurement methods and values, and monitoring by Is usually is now recommended in the guidelines of various countries [83,84]. However, molecular relapse is experienced in more than 50% of patients undergoing TKI discontinuation, even after achieving deep and undetectable MRD as measured by the BCR-ABL1 mRNA test [85,86,87]. This suggests that the currently used MRD measurement may be insufficient as it is unable to detect leukemic cells lurking in the bone marrow microenvironment. By measuring the expression of BCR-ABL in CML cell-derived exosomes, it could be possible to evaluate residual CML cells in the bone marrow microenvironment, thus exposing the potential role of exosomes as biomarkers. Another significant role of exosomes issues the in vivo delivery of drugs, microRNA, and other molecules. Due to their noninvasive nature and easy convenience, as well as the fact INCB054329 Racemate that microRNAs can evade destruction in guarded spaces such as exosomes, the latter have emerged as a potentially new therapeutic strategy. The role of exosome-derived leukemia has been extensively analyzed. Exosomes play numerous functions in the progression of leukemia, including regulation of the bone marrow microenvironment and angiogenesis; inhibition of hematopoiesis, metastasis to other organs, and immune escape; and transformation of the microenvironment into a tumorigenic microenvironment. Thus, an in-depth understanding of the broad roles played by leukemic exosomes will lead to a better understanding of the pathogenesis of leukemia and will yield important new perspectives not only concerning the development of new therapies to eliminate relapse but also early diagnosis and early detection of relapse. 3.2. Bone Marrow Remodeling by Leukemic Exosomes Leukemic cell-derived exosomes play an important role in the remodeling of the bone marrow microenvironment [88] by regulating the communication between leukemic cells and the bone marrow microenvironment (Physique 2). Open in a separate window Physique 2 Interactions between leukemic exosomes and their niches. Shown are the multiple regulatory mechanisms implicated in promoting leukemic cell survival. Those that promote the function of the target cells (blue) and those that inhibit it (reddish) are INCB054329 Racemate depicted, respectively. Leukemia cells promote their own proliferation by the exosomes they secrete. The exosomes derived from leukemic cells inhibit the normal hematopoiesis of hematopoietic stem cells (HSCs), inhibit the differentiation of mesenchymal stromal cells (MSCs), and promote their own proliferation. In addition, they promote osteolineage cell activity as Sema3b well as their own proliferation. Closer to the vascular endothelium, they promote angiogenesis, which allows for their own proliferation and migration to other organs. In the case of adipose tissue, exosomes interfere with adipogenesis and alter their functionality as a source of energy.