salicylates and Leukemia--Myeloid--Acute

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.. 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.. Choline magnesium trisalicylate +/- dexamethasone decreased nuclear NF-kappaB, whereas dexamethasone alone was associated with an increase in nuclear NF-kappaB in AML cells.. 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.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Nucleus; Choline; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; NF-kappa B; Salicylates

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Choline; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute; NF-kappa B; Salicylates; Signal Transduction; Treatment Outcome

A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations.

Topics: Adolescent; Adult; Age Factors; Aged; Appendectomy; Case-Control Studies; China; Disease; Female; Humans; Hyperthyroidism; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Salicylates; Tuberculosis

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Leukemia, Myeloid, Acute; Neoplasms; Prostaglandins A; Prostaglandins E; Salicylates