NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia.
Sci Rep
; 10(1): 10315, 2020 06 25.
Article
in En
| MEDLINE
| ID: mdl-32587277
ABSTRACT
Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio 3.6; 95% Confidence Interval 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Promyelocytic, Acute
/
Antineoplastic Combined Chemotherapy Protocols
/
Adaptor Proteins, Signal Transducing
Type of study:
Observational_studies
/
Risk_factors_studies
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
Brazil