Overcoming treatment resistance in acute promyelocytic leukemia and beyond

Tsz Kan Fung,Chi Wai Eric So

doi:10.18632/oncotarget.1244

Abstract

Overcoming treatment resistance in acute promyelocytic leukemia and beyond

Highlights

From the introduction of all-trans retinoic acid (ATRA) to the recent development of arsenic trioxide (ATO) treatment, acute promyelocytic leukemia (APL) characterized by the presence of retinoic acid receptor alpha (RARA) fusion has been transformed from a highly fatal cancer to a highly curable disease
A prolonged ATRA treatment can result in drug resistance by inducing and/ or selecting leukemic clones carrying mutations on the ligand binding domain (LBD) of the RARA moiety or aberrant transcription repression complexes that could not be dissociated by ATRA treatment (Figure 1b), which are commonly found in relapse cases
ATO has been successfully used both in combination with ATRA for induction therapy and as a second line treatment for ATRA-resistance, mutations on the PML moiety of the RARA fusion affecting the ATO-induced protein degradation can be found in APL cells after ATO treatment (Figure 1d)

Summary

Introduction

From the introduction of all-trans retinoic acid (ATRA) to the recent development of arsenic trioxide (ATO) treatment, acute promyelocytic leukemia (APL) characterized by the presence of retinoic acid receptor alpha (RARA) fusion has been transformed from a highly fatal cancer to a highly curable disease. A prolonged ATRA treatment can result in drug resistance by inducing and/ or selecting leukemic clones carrying mutations on the ligand binding domain (LBD) of the RARA moiety or aberrant transcription repression complexes that could not be dissociated by ATRA treatment (Figure 1b), which are commonly found in relapse cases.

Results

Conclusion