Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia.
BACKGROUND
The Wilms Tumor gene (WT1) encodes a transcription factor involved in kidney development and malignancy. WT1 expression in a subpopulation of early CD34+ cells has suggested its involvement in hematopoiesis. WT1 is aberrantly expressed in leukemias. High expression of WT1 at diagnosis has been associated with unfavorable prognosis in adult acute myeloid leukemia (AML). The prognostic relevance of WT1 expression in pediatric AML was evaluated in only one study, including 47 patients, which showed that very low levels of WT1 at presentation were associated with an excellent outcome. To test the validity of these findings we measured levels of WT1 in 41 newly diagnosed pediatric AML of the non-M3 FAB subtype.


METHODS
Patients were treated according to an AML-BFM 83-based protocol in a single institution. Mononucleated cells obtained from presentation BM aspirates were cryopreserved and later thawed and used for total RNA extraction and cDNA synthesis. The quantitative assessment of WT1 transcripts was made by real-time PCR (RQ-PCR). WT1 transcripts values were normalized with respect to the number of ABL transcripts.


RESULTS
WT1 levels were significantly higher in patients bearing favorable chromosome abnormalities, t(8;21) and inv(16) (P = 0.002). Higher levels of WT1 expression were unexpectedly associated with a higher probability of overall survival by Cox regression analysis (P = 0.002). Multivariate regression analysis could not discriminate between the effects of WT1 and cytogenetics on survival.


CONCLUSIONS
Higher WT1 expression was associated with favorable cytogenetics subtypes and accordingly with better outcome in children with AML in this study.
Rodrigues
Patricia C
PC
Laboratório de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil.
Oliveira
Sátiro N
SN
Viana
Marcos B
MB
Matsuda
Eduardo I
EI
Nowill
Alexandre E
AE
Brandalise
Silvia R
SR
Yunes
José A
JA
D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D016162:Genes, Wilms Tumor; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000401:mortality; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014178:Translocation, Genetic; D025721:WT1 Proteins / Q000096:biosynthesis
D009363:Neoplasm Proteins; D025721:WT1 Proteins; D003561:Cytarabine; D005047:Etoposide; D003630:Daunorubicin