High expression of TARP correlates with inferior FLT3 mutations in non-adolescents and young adults with acute myeloid leukaemia

Abstract

Objectives: Acute myeloid leukaemia (AML) is a haematopoietic malignancy with a dismal outcome. Consequently, risk stratification based on more effective prognostic biomarkers is crucial to make accurate therapy decisions. T cell receptor gamma alternative reading frame protein (TARP) has been reported in prostate and breast cancers, but its correlation with AML remains unclear. Methods: Differential expression of TARP mRNA in different AML subtypes was analysed using the UALCAN online platform. Its relationship with baseline clinical attributes, survival and efficacy were analysed based on three GSE1159, GSE425 and GSE6891 microarray datasets downloaded from Gene Expression Omnibus (GEO) and Oncomine databases. Quantitative real-time PCR was performed to determine mRNA levels of TARP in bone marrow mononuclear cells (BMMCs) isolated from AML patients. Results: TARP was significantly overexpressed in AML patients. In AML, relatively low TARP expression was associated with the CBFβ-MYH11 fusion gene. The proportion of FLT3 mutations was significantly higher in non-adolescent and young adult (non-AYA, >39 years of age) AML patients who had high TARP levels but not in AYA (15-39 years) patients. High expression of TARP was related to poor outcome by univariate analysis but not by multivariate analysis and unsatisfactory therapeutic effects, which could be overcome by haematopoietic stem cell transplantation (HSCT). Conclusion: Our findings suggest that TARP might be a potential prognostic marker of AML and serve as a promising immunotherapeutic target.

Single-cell analysis of pediatric acute myeloid leukemia samples uncovers treatment-resistant stem and mast cells

“…RUNX1 HRTR overexpress CD69 and IGLL1, a gene typically associated with B cells, that has been reported as enriched in relapsed pAML 8 . FLT3 HRTR pAML overexpressed CD69 and TRGC2, an isotype of the TARP protein previously described as a poor prognostic indicator and LSC marker in FLT3 pAML 44,63 . CD69 + IGLL1 + HSC-like pAML manifests resistance by over-expressing genes related to proliferative and immune remodeling pathways, while CD69 + TRGC2 + HSC-like pAML utilizes antioxidant metabolism.…”