en
Scientific article
Open access
English

Clinical significance of ABCB1 in acute myeloid leukemia : a comprehensive study

Published inCancers, vol. 11, no. 9, 1323
Publication date2019-09-06
Abstract

ABCB1 is a member of the ATP binding cassette transporter family and high ABCB1 activity is considered as a poor prognostic factor in acute myeloid leukemia (AML) treated with intensive chemotherapy, its direct relation with drug resistance remains unclear. We evaluated ABCB1 activity in relation with clinical parameters and treatment response to standard chemotherapy in 321 patients with de novo AML. We assessed multiple clinical relationships of ABCB1 activity-ex vivo drug resistance, gene expression, and the ABCB1 inhibitor quinine were evaluated. ABCB1 activity was observed in 58% of AML and was linked to low white blood cell count, high expression of CD34, absence of FLT3-ITD, and absence of mutant NPM1. Moreover, ABCB1 activity was associated with worse overall- and event-free survival. However, ABCB1 activity did not directly lead to ex vivo drug resistance to anthracyclines. We found that ABCB1 was highly correlated with gene expressions of BAALC, CD34, CD200, and CD7, indicating that ABCB1 expression maybe a passenger characteristic of high-risk AML. Furthermore, ABCB1 was inversely correlated to HOX cluster genes and CD33. Thus, low ABCB1 AML patients benefited specifically from anti-CD33 treatment by gemtuzumab ozogamicin in addition to standard chemotherapy. We showed prognostic importance of ABCB1 gene expression, protein expression, and activity. Furthermore, ABCB1 was not directly linked to drug resistance, ABCB1 inhibition did not improve outcome of high ABCB1 AML patients and thus high ABCB1 may represent a passenger characteristic of high-risk AML.

eng
Keywords
  • ABCB1
  • Acute myeloid leukemia
  • Drug resistance
  • Gene expression
  • Prognosis
Affiliation Not a UNIGE publication
Citation (ISO format)
BOYER, Thomas et al. Clinical significance of ABCB1 in acute myeloid leukemia : a comprehensive study. In: Cancers, 2019, vol. 11, n° 9, p. 1323. doi: 10.3390/cancers11091323
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1968-0694
17views
2downloads

Technical informations

Creation03/19/2024 9:33:07 AM
First validation05/23/2024 8:26:45 AM
Update time05/23/2024 8:26:45 AM
Status update05/23/2024 8:26:45 AM
Last indexation05/23/2024 8:27:06 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack