PURPOSE: Nuclear factor-kappaB (NF-kappaB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-kappaB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-kappaB when administered in conjunction with induction chemotherapy. EXPERIMENTAL DESIGN: Patients with newly diagnosed AML were treated with dexamethasone, choline magnesium trisalicylate, or both for 24 hours prior to and 24 hours following initiation of standard induction chemotherapy. AML cell nuclear NF-kappaB was measured at baseline, 24, and 48 hours. RESULTS: Choline magnesium trisalicylate +/- dexamethasone decreased nuclear NF-kappaB, whereas dexamethasone alone was associated with an increase in nuclear NF-kappaB in AML cells. CONCLUSIONS: These results show the feasibility of NF-kappaB modulation in conjunction with induction chemotherapy for patients with AML using inexpensive readily available medications. A follow-up study to determine the effects of NF-kappaB modulation on clinical end points is warranted.
PURPOSE:Nuclear factor-kappaB (NF-kappaB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-kappaB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-kappaB when administered in conjunction with induction chemotherapy. EXPERIMENTAL DESIGN:Patients with newly diagnosed AML were treated with dexamethasone, choline magnesium trisalicylate, or both for 24 hours prior to and 24 hours following initiation of standard induction chemotherapy. AML cell nuclear NF-kappaB was measured at baseline, 24, and 48 hours. RESULTS:Choline magnesium trisalicylate +/- dexamethasone decreased nuclear NF-kappaB, whereas dexamethasone alone was associated with an increase in nuclear NF-kappaB in AML cells. CONCLUSIONS: These results show the feasibility of NF-kappaB modulation in conjunction with induction chemotherapy for patients with AML using inexpensive readily available medications. A follow-up study to determine the effects of NF-kappaB modulation on clinical end points is warranted.
Authors: Daniel J Medina; Lauri Goodell; John Glod; Céline Gélinas; Arnold B Rabson; Roger K Strair Journal: Haematologica Date: 2012-02-27 Impact factor: 9.941
Authors: Rehan Ahmad; Suiyang Liu; Ellen Weisberg; Erik Nelson; Ilene Galinsky; Colin Meyer; Donald Kufe; Surender Kharbanda; Richard Stone Journal: Mol Cancer Res Date: 2010-06-22 Impact factor: 5.852