In vitro down-regulation of bcl-2 expression by all-trans retinoic acid in AML blasts.
Using flow cytometry, we have investigated the effects of 0.5 microM all-trans-retinoic acid (ATRA) on bcl-2 expression in the blast cells of 25 acute myeloblastic leukemia (AML) patients and the HL-60 cell line after incubation for 6 days. We observed a significant decrease of bcl-2 expression after treatment with ATRA in 12 of 25 AML samples and the HL-60 cells. The mean fluorescence intensity (MFI) ratio for the bcl-2 levels of the ATRA responders (n = 12) was reduced to 7.9 +/- 4.8 following incubation with ATRA compared with 10.9 +/- 6.5 (mean +/- SD) for control samples incubated without ATRA (p = 0.011). There was no significant difference between the baseline bcl-2 MFI ratio in the ATRA responders (11.14 +/- 7, n = 12) and the non responders (14.18 +/- 11.3, n = 13; p = 0.432). The down-regulation of bcl-2 expression by ATRA was not significantly associated with CD34-negative or -positive AML. There was no correlation between AML subtypes and regulation of bcl-2 expression by ATRA. Complete remission and overall survival were not significantly improved in bcl-2 down-regulated cases. Our data confirm that ATRA can down-regulate the bcl-2 expression in AML blasts. Because many chemotherapeutic agents also operate through the activation of programmed cell death and bcl-2 levels are positively associated with resistance to apoptosis, ATRA can be used in combination chemotherapy to increase the chemosensitivity of some patients with AML.
Pisani
F
F
Department of Hematology, University Tor Vergata, St. Eugenio Hospital, Rome, Italy.
Del Poeta
G
G
Aronica
G
G
Venditti
A
A
Caravita
T
T
Amadori
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014212:Tretinoin