Recent Progress of Exosomes in Hematological Malignancies: Pathogenesis, Diagnosis, and Therapeutic Strategies

Abstract

Hematological malignancies originate from the hematopoietic system, including lymphoma, multiple myeloma, leukaemia, etc. They are highly malignant with a high incidence, a poor prognosis and a high mortality. Although the novel therapeutic strategies have partly improved the clinical efficacy of hematological malignancies, patients still face up with drug resistance, refractory disease and disease relapse. Many studies have shown that exosomes play an important role in hematological malignancies. Exosomes are nanoscale vesicles secreted by cells with a size ranging from 40 to 160 nm. They contain various intracellular components such as membrane proteins, lipids, and nucleic acids. These nanoscale vesicles transmit information between cells with the cargos. Thus, they participate in a variety of pathological processes such as angiogenesis, proliferation, metastasis, immunomodulation and drug resistance, which results in important role in the pathogenesis and progression of hematological malignancies. Furthermore, exosomes and the components carried in them can be used as potential biomarkers for the diagnosis, therapeutic sensitivity and prognosis in hematological malignancies. In the therapy of hematologic malignancies, certain exosome are potential to be used as therapeutic targets, meanwhile, exosomes are suitable drug carriers with lipid bilayer membrane and the nanostructure. Moreover, the tumor-derived exosomes of patients with hematologic malignancies can be developed into anti-tumor vaccines. The research and application of exosomes in hematological malignancies are summarized and discussed in this review.

Keywords: biomarkers; drug carriers; exosomes; hematological malignancies; targets; vaccines.

Figure 1

Timeline of exosome research milestones.

Figure 2

Biogenesis of exosomes: exosomes can originate from humans, animals, plants, and bacteria. In humans, exosomes are widely distributed and can be found in peripheral blood, cerebrospinal fluid, saliva, urine, milk, etc. The endocytosis of the plasma membrane leads to the formation of endocytic vesicles, which fuse to form early endosomes. Early endosomes further mature into late endosomes. The late endosome membrane buds inward, forming ILVs. Many ILVs compose the MVBs. The MVBs further fuse with the cell surface membrane and release their ILVs, termed exosomes.

Figure 3

Components of exosomes: Exosomes contain ingredients from the cell, including lipids, nucleic acids, and proteins. Lipids include phospholipids, Ganglioside GM3, cholesterol, etc. Nucleic acids encompass DNA and RNA. Proteins include tetraspanin proteins (CD9, CD63, CD81, CD82), cell adhesion molecules (integrins, CD11b, CD54), MHC molecules (MHC-I, MHC-II), fusion and transport proteins (Rab2, Rab7, flotillin), heat shock proteins (Hsc70, Hsc90), and proteins that mediate the formation of MVBs (ALIX).

Figure 4

The roles of exosomes in hematological malignancies. Exosomes effectively manipulate tumor microenvironment in hematological malignancies, influencing the processes of angiogenesis, proliferation, immune regulation and drug resistance. Thus they can lead to the pathogenesis and development of hematological malignancies. Exosomes have been studied and recognized as potential biomarkers for diagnosis and prognosis in hematological malignancies due to their abilities to reflect the physiological and pathological state of their cells of origin. Meanwhile exosomes are potential to be used in therapeutic strategies for hematological malignancies as therapeutic targets, drug carriers and vaccines.