Nuclear factor-kappaB modulation in patients undergoing induction chemotherapy for acute myelogenous leukemia.
OBJECTIVE
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.


METHODS
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.
Strair
Roger K
RK
Division of Medical Oncology, The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA. strairrk@umdnj.edu
Gharibo
Mecide
M
Schaar
Dale
D
Rubin
Arnold
A
Harrison
Jonathan
J
Aisner
Joseph
J
Lin
Hsin-Ching
HC
Lin
Yong
Y
Goodell
Lauri
L
Anand
Monika
M
Balsara
Binaifer
B
Dudek
Liesel
L
Rabson
Arnold
A
Medina
Daniel J
DJ
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003907:Dexamethasone / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis* / Q000187:drug effects; D012459:Salicylates / Q000008:administration & dosage*
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D012459:Salicylates; D003907:Dexamethasone; C017959:choline magnesium trisalicylate; D002794:Choline