Stay Connected. Manage Your Care.
Access your health information anytime and anywhere, at home or on the go, with MyHealth.
- Message your clinic
- View your lab results
- Schedule your next appointment
- Pay your bill
The MyHealth mobile app from Stanford Health Care puts all your health information at your fingertips and makes managing your health care simple and quick.
Guest Services
24/7
We are available to assist you
whenever you need it. Give us a call at
650-498-3333 or
PHYSICIAN HELPLINE
Have a question? We're here to help! Call 1-866-742-4811
Monday - Friday, 8 a.m. - 5 p.m.
REFER A PATIENT
Fax 650-320-9443
Track your patients' progress and communicate with Stanford providers conveniently and securely.
Abstract
Mutations in exon 12 of the NPM1 gene (NPMc+) define a distinct subset of acute myelogenous leukemias (AML) in which the NPMc+ protein localizes aberrantly to the leukemic cell cytoplasm. We have found that introduction of the most common NPMc+ variant into K562 and 32D cells sensitizes these cells to apoptosis induced by drugs such as bortezomib and arsenic trioxide that induce reactive oxygen species (ROS) formation and that cytotoxicity is prevented in the presence of N-acetyl-1-cysteine, a ROS scavenger. The substitution of tryptophan288 by cysteine occurs in the great majority of NPM1c+ mutations. Mutagenesis of C288 to alanine re-localizes NPMc+ from the cytoplasm to the nucleolus and attenuates the sensitivity of cells expressing this mutation to bortezomib and arsenic trioxide. Primary AML leukemic cells expressing NPMc+ are also significantly more sensitive than other AML cells to apoptosis induced by both drugs at pharmacologically achievable doses. We conclude that the presence of a cysteine moiety at position 288 results in the cytoplasmic localization of NPM1c+ and the increased sensitivity to bortezomib and arsenic trioxide. These data suggest that bortezomib and arsenic trioxide may have increased therapeutic efficacy in NPM1c+ leukemias.Leukemia accepted article preview online, 23 July 2013. doi:10.1038/leu.2013.222.
View details for DOI 10.1038/leu.2013.222
View details for Web of Science ID 000325642600003