Low 25(OH) Vitamin D3 Levels Are Associated With Adverse Outcome in Newly Diagnosed, Intensively Treated Adult Acute Myeloid Leukemia

被引:51
作者
Lee, Hun Ju [1 ]
Muindi, Josephia R. [2 ]
Tan, Wei [3 ]
Hu, Qiang [3 ]
Wang, Dan [3 ]
Liu, Song [3 ]
Wilding, Gregory E. [3 ]
Ford, Laurie A. [1 ]
Sait, Sheila N. J. [4 ]
Block, Annemarie W. [4 ]
Adjei, Araba A. [2 ]
Barcos, Maurice [5 ]
Griffiths, Elizabeth A. [1 ]
Thompson, James E. [1 ]
Wang, Eunice S. [1 ]
Johnson, Candace S. [2 ]
Trump, Donald L. [6 ]
Wetzler, Meir [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Med, Leukemia Sect, Buffalo, NY 14263 USA
[2] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA
[3] Roswell Pk Canc Inst, Dept Biostat, Buffalo, NY 14263 USA
[4] Roswell Pk Canc Inst, Clin Cytogenet Lab, Buffalo, NY 14263 USA
[5] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA
[6] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA
关键词
acute myeloid leukemia; vitamin D; single nucleotide polymorphism; microRNA; outcome; D INSUFFICIENCY; D-RECEPTOR; MONOCYTIC DIFFERENTIATION; FUNCTIONAL GENOMICS; MAPK PATHWAYS; HL60; CELLS; CANCER; GENE; ACTIVATION; PROGNOSIS;
D O I
10.1002/cncr.28368
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUNDSeveral studies have suggested that low 25(OH) vitamin D-3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML). METHODSVitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D-3 pathway genes were evaluated and correlated with 25(OH) vitamin D-3 levels and treatment outcome. RESULTSThirty-four patients (35%) had normal 25(OH) vitamin D-3 levels (32-100 ng/mL), 34 patients (35%) had insufficient levels (20-31.9 ng/mL), and 29 patients (30%) had deficient levels (<20 ng/mL). Insufficient/deficient 25(OH) vitamin D-3 levels were associated with worse relapse-free survival (RFS) compared with normal vitamin D-3 levels. In multivariate analyses, deficient 25(OH) vitamin D-3, smoking, European Leukemia Network genetic group, and white blood cell count retained their statistical significance for RFS. Several microRNAs and SNPs were associated with 25(OH) vitamin D-3 levels, although none remained significant after multiple test corrections; one 25(OH) vitamin D-3 receptor SNP, rs10783219, was associated with a lower complete remission rate (P=.0442) and with shorter RFS (P=.0058) and overall survival (P=.0011). CONCLUSIONSIt remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D-3 level and/or outcome and whether supplementation will improve outcomes for patients with AML. Cancer 2014;120:521-529. (c) 2013 American Cancer Society.
引用
收藏
页码:521 / 529
页数:9
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