Human Voltage-Activated H+ Channel is Highly Expressed in Acute Myeloid Leukemia and is Associated With the Blast Differentiated Stage

Abstract

Background

In acute myeloid leukemia (AML), hematopoietic precursors of myeloid cells proliferate rapidly but are arrested at an early stage, impeding their maturation and normal function. The human voltage-activated proton channel (hHv1) is a membrane protein with important roles in myeloid phagocytic cells. This work aimed to evaluate the expression of hHv1 channel as a novel biological marker associated with the process of cell differentiation in AML.

Methods

In this study, we evaluated the expression of the hHv1, at both mRNA and protein levels in AML.

Results

We demonstrated that the expression of hHv1 is upregulated at both mRNA and protein levels in AML. Moreover, our results indicate that hHv1 expression correlates with the degree of monocytic differentiation in AML cells in a pattern similar to that previously reported for NADPH oxidase (NOX2), a relevant cellular structure functionally coupled to the hHv1 channel. However, while increases in NOX2 components have not been associated with improved prognosis or survival, we found that the hHv1 upregulation was associated with better prognosis and survival outcomes.

Conclusions

These results suggest that hHv1 may serve as a novel biomarker for favorable prognosis in AML and may represent a promising therapeutic target.