Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia.
Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4 %) patients. At least one copy of the minor SNP rs16754 allele (WT1(AG) or WT1(GG)) was detected in 30 (29 %) patients. Six patients (6 %) were homozygous for the minor allele (WT1(GG)) and this genotype was associated with higher WT1 mRNA copies (p = 0.018). FLT3 mutations were found in 37 % of patients and correlated with high WT1 mRNA expression (p = 0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1(AA)) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.
Department of Biopathology, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
Girish Chander
GC
Gaur
Safaa M
SM
Ramadan
Laura
L
Cicconi
Nélida I
NI
Noguera
Irene
I
Luna
Esperanza
E
Such
Serena
S
Lavorgna
Jonny
J
Di Giandomenico
Miguel A
MA
Sanz
Francesco
F
Lo-Coco
D000328:Adult; D018389:Codon, Nonsense; D015331:Cohort Studies; D016368:Frameshift Mutation; D015973:Gene Expression Regulation, Leukemic; D056726:Genetic Association Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D012384:Rome; D013030:Spain; D016019:Survival Analysis; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
D018389:Codon, Nonsense; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins