Effect of cis-retinoic acid on bcl-2 and some mitochondrial enzymes in patients with acute myeloid leukemia : A randomized cytochemical study

Abstract EN

Background : Cis retinoic acid (Cis-RA) is one of the retinoids, which induce growth arrest and apoptosis in acute myeloblastic leukemia (AML(.

Aim : The present work aimed to investigate whether Cis-RA- induced apoptosis in AML is related to changes in BcL-2 oncoprotein and some mitochondrial enzymes, notably cytochrome C oxidase and adenosine triphosphatase (ATPase) in patients with acute myeloid leukemia (AML).

Methods: Thirty patients with AML were enrolled in the study.

Ten healthy individuals served as control.

Bone marrow smears were collected before and after chemotherapy, cyto-chemistry for cytochrome C oxidase and ATPase and immunocytochemistry of Bcl-2 were done.

Results : The present work revealed that the cytochrome C oxidase activity was reduced in patients before chemotherapy compared to the control.

while, it was strong after chemotherapy (with or without Cis-RA) reflecting apoptosis.

Weak ATPase activity was found in patients versus the control due to its depletion.

Bcl-2 was overexpressed in patients versus the control, decreased after chemotherapy, especially in patients who received Cis-RA and remained high in patients exhibiting drug resistance.

A significant reduction of bcl-2 (P<0.001) paralleled with a significantly positive reaction of cytochrome C oxidase (P<0.001).

Conclusions : It is concluded that Cis-RA reduces Bcl-2 activity and increases the release of cytochrome C oxidase with depletion of ATPase.