The role of exosomes and MYC in therapy resistance of acute myeloid leukemia: Challenges and opportunities

Publication date: Available online 14 October 2019Source: Molecular Aspects of MedicineAuthor(s): Nithya Mudgapalli, Palanisamy Nallasamy, Haritha Chava, Srinivas Chava, Anup S. Pathania, Venugopal Gunda, Santhi Gorantla, Manoj K. Pandey, Subash C. Gupta, Kishore B. ChallagundlaAbstractAcute myeloid leukemia (AML) is caused by abnormal production of white blood cells, red blood cells or platelets. The leukemia cells communicate with their microenvironment through nano-vesicle exosomes that are 30–100 nm in diameter. These nano-vesicles are released from body fluids upon fusion of an endocytic compartment with the cell membrane. Exosomes function as cargo to deliver signaling molecules to distant cells. This allows cross-talk between hematopoietic cells and other distant target cell environments. Exosomes support leukemia growth by acting as messengers between tumor cells and the microenvironment as well as inducing oncogenic factors such as c-Myc. Exosomes have also been used as biomarkers in the clinical diagnosis of leukemia. Glycogen synthase kinase-3 (GSK-3) and protein phosphatase 2A (PP2A) are two crucial signaling molecules involved in the AML pathogenesis and MYC stability. GSK-3 is a serine/threonine protein kinase that coordinates with over 40 different proteins during physiological/pathological conditions in blood cells. The dysregulation in GSK-3 has been reported during hematological malignancies. GSK-3 acts as a tumor suppressor by targeting c-MYC, MCL-1 and...
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research