1. Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5'-nucleotidase
- Author
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Ingrid Jakobsen Falk, Kourosh Lotfi, Henrik Gréen, Monica Hermanson, Richard Rosenquist, Lars Palmqvist, Hareth Nahi, Esbjorn Paul, Dick Stockelberg, Yuan Wei, Martin Höglund, and Anna Fyrberg
- Subjects
Male ,Medicin och hälsovetenskap ,Kaplan-Meier Estimate ,Medical and Health Sciences ,5'-nucleotidase ,fluids and secretions ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,5'-Nucleotidase ,Aged, 80 and over ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Karyotype ,Hematology ,Cytidine deaminase ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Neoplasm Proteins ,Leukemia, Myeloid, Acute ,Tandem Repeat Sequences ,Inactivation, Metabolic ,Female ,Nucleophosmin ,medicine.drug ,Adult ,Antimetabolites, Antineoplastic ,Adolescent ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Young Adult ,Cytidine Deaminase ,Deoxycytidine Kinase ,medicine ,Humans ,Gene ,Aged ,Proportional Hazards Models ,Daunorubicin ,DNA Methylation ,Survival Analysis ,fms-Like Tyrosine Kinase 3 ,Drug Resistance, Neoplasm ,Fms-Like Tyrosine Kinase 3 ,Cancer research ,Topoisomerase I Inhibitors ,Idarubicin - Abstract
De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and −451C>T rs532545), 5′-nucleotidase (cN-II 7A>G rs10883841), and deoxycytidine kinase (DCK 3′UTR 948T>C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem duplication (ITD)-positive patients, the CDA 79C/C and −451T/T genotypes were associated with shorter overall survival compared to other genotypes (5 vs. 24 months, P
- Published
- 2013