TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes

• Published in: The New England journal of medicine Vol. 375; no. 21; pp. 2023 - 2036
• Main Authors: Welch, John S, Petti, Allegra A, Miller, Christopher A, Fronick, Catrina C, O’Laughlin, Michelle, Fulton, Robert S, Wilson, Richard K, Baty, Jack D, Duncavage, Eric J, Tandon, Bevan, Lee, Yi-Shan, Wartman, Lukas D, Uy, Geoffrey L, Ghobadi, Armin, Tomasson, Michael H, Pusic, Iskra, Romee, Rizwan, Fehniger, Todd A, Stockerl-Goldstein, Keith E, Vij, Ravi, Oh, Stephen T, Abboud, Camille N, Cashen, Amanda F, Schroeder, Mark A, Jacoby, Meagan A, Heath, Sharon E, Luber, Kierstin, Janke, Megan R, Hantel, Andrew, Khan, Niloufer, Sukhanova, Madina J, Knoebel, Randall W, Stock, Wendy, Graubert, Timothy A, Walter, Matthew J, Westervelt, Peter, Link, Daniel C, DiPersio, John F, Ley, Timothy J
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 24.11.2016
• Subjects: 5-aza-2'-deoxycytidine; 5-Methylcytosine - analysis; Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Azacitidine - administration & dosage; Azacitidine - adverse effects; Azacitidine - analogs & derivatives; Biomarkers; Biomarkers, Tumor - analysis; Blood diseases; Bone marrow; Bone Marrow - chemistry; Bone Marrow - pathology; Chemotherapy; Clinical outcomes; Decitabine; Exome; Female; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Male; Middle Aged; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Myeloid leukemia; p53 Protein; Prospective Studies; Risk Factors; Survival; Survival Rate; Tumor Suppressor Protein p53 - genetics
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1605949

Decitabine produced responses in patients with acute myeloid leukemia or myelodysplastic syndromes who had cytogenetic abnormalities associated with a poor prognosis, including 21 of 21 patients with tumors that contained TP53 mutations. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are clonal disorders of myeloid hematopoiesis. 1 Adult patients with AML who have karyotypes that are associated with unfavorable risk and older patients with AML (≥60 years of age) have poor outcomes, with a median survival of approximately 1 year. 2 , 3 Patients with AML and TP53 mutations tend to be older (median age, 61 to 67 years), and almost all have karyotypes that are associated with unfavorable risk; if they receive standard cytotoxic chemotherapy, these patients have especially poor outcomes (median survival, 4 to 6 months). 3 – 6 Decitabine (5-aza-2′-deoxycytidine) is commonly used as . . .