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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Source:
Title:

Anti-Apoptotic BCL-2 Family Members Confer Resistance to Calicheamicin-Based Antibody-Drug Conjugate Therapy of Acute Leukemia

Published date:
11/06/2019
Excerpt:
At a dose of 1000 pg/ml, GO killing of ML-1 (AML) cells decreased from 56±5% (mean±SEM) in parental cells to 32±7% (p<0.01) and 26±6% (p<0.01) in cells overexpressing BCL-2 and BCL-XL, respectively (all n=3)…AZD5991 modestly increased the anti-leukemic efficacy of GO in ML-1 cells and AML patient specimens, but more dramatically enhanced IO killing of REH cells (IO at 10 pg/ml....though the triplet combination of IO, ABT-199 and AZD5991 showed promising activity: in REH cells treated with 10 pg/ml IO, cytotoxicity was 18±2% without BCLi, 32±8% with ABT-199 0.1 µM, 19±2% with AZD5991 0.01 µM, and 56±14% with the triplet combination (p<0.01 for comparison of triplet combination with IO/BCLi doublet).
DOI:
https://doi.org/10.1182/blood-2019-126110