Evaluation of noncytotoxic DNMT1-depleting therapy in patients with myelodysplastic syndromes

• Published in: The Journal of clinical investigation Vol. 125; no. 3; pp. 1043 - 1055
• Main Authors: Saunthararajah, Yogen, Sekeres, Mikkael, Advani, Anjali, Mahfouz, Reda, Durkin, Lisa, Radivoyevitch, Tomas, Englehaupt, Ricki, Juersivich, Joy, Cooper, Kathleen, Husseinzadeh, Holleh, Przychodzen, Bartlomiej, Rump, Matthew, Hobson, Sean, Earl, Marc, Sobecks, Ronald, Dean, Robert, Reu, Frederic, Tiu, Ramon, Hamilton, Betty, Copelan, Edward, Lichtin, Alan, Hsi, Eric, Kalaycio, Matt, Maciejewski, Jaroslaw
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.03.2015
• Subjects: Aged; Aged, 80 and over; Analysis; Antimetabolites, Antineoplastic - administration & dosage; Apoptosis; Azacitidine - administration & dosage; Azacitidine - analogs & derivatives; Biomedical research; Cancer; Cancer therapies; Care and treatment; Clinical Medicine; Clinical trials; Cytotoxicity; Decitabine; Deoxyribonucleic acid; DNA; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors; DNA (Cytosine-5-)-Methyltransferases - metabolism; Drug Administration Schedule; Drug dosages; Enzymes; Female; Gene expression; Humans; Hypotheses; Leukemia; Male; Middle Aged; Mortality; Mutation; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - mortality; Oncology, Experimental; Response rates; Stem cells; Studies; Survival Analysis; Transcription factors; Treatment Outcome

Mutational inactivation in cancer of key apoptotic pathway components, such as TP53/p53, undermines cytotoxic therapies that aim to increase apoptosis. Accordingly, TP53 mutations are reproducibly associated with poor treatment outcomes. Moreover, cytotoxic treatments destroy normal stem cells with...