Acute myeloid leukemia: Therapy resistance and a potential role for tetraspanin membrane scaffolds

Abstract

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family of proteins often serve as signaling mediators, translating extracellular signaling cues into intracellular signaling cascades. In this review, we discuss the conventional and targeted treatment strategies for AML and review chemoresistance mechanisms with a focus on the tetraspanin family of membrane scaffold proteins.

Keywords: Acute myeloid leukemia; Chemoresistance; Targeted therapy; Tetraspanins.

Fig. 1.

Tetraspanins regulate AML chemoresistance and survival signaling. Schematic of the AML membrane depicting different tetraspanins (CD9, CD82, CD81, TSPAN3) along with proposed signaling mechanisms involved in AML chemoresistance and survival. Created using BioRender.