In:
Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4911-4911
Abstract:
All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. For subsequent similar data, NCCN guidelines indicate that ATRA plus ATO is an alternative for patients who cannot tolerate anthracycline therapy. We demonstrated that SFK (Src Family Kinase) inhibitor PP2 enhanced acute promyelocytic leukemia (APL) cell differentiation when combined with either ATRA or ATO with difference in activation of RA-induced genes. In this study, we investigated SFK inhibitor PP2 could enhances the differentiation of NB4 APL cells when combined with ATRA and ATO and the changes in the expression of intercellular adhesion molecule-1 (ICAM-1) derived from the retinoic acid receptor (RAR) target gene. Treatment of NB4 cells with 1 nM of ATRA, 0.5 uM of ATO, or 10 uM of PP2 for 72 hours induced expression of CD11b-positive cells by 13.01%, 11.53% or 13.28%, respectively. However, the combination of ATRA and ATO and the combination of three agents (ATRA, ATO, and PP2) led to a significant higher expression of CD11b-positive cells (30.96% and 63.17%, respectively). The synergistic effect of the combination of three agents was more significant than the combination of ATRA and ATO. These results were confirmed by NBT staining. These effects were not related with apoptosis. Annexin-V-fluorescene staining revealed that combination of ATRA and ATO and combination of three agents did not induced apoptosis in NB4 cells. The expression of ICAM-1 was markedly increased in cells treated with the combination of three agents. These findings suggest that the SFK inhibitor can enhances differentiation of APL cells combined with ATRA and ATO. FDA approved SFK inhibitors, such as dasatinib and bosutinib, may be beneficial for the treatment of APL in combination with ATRA and ATO. Disclosures: No relevant conflicts of interest to declare.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V122.21.4911.4911
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2013
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
