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Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia
Author(s) -
Rodrigues Patricia C.,
Oliveira Sátiro N.,
Viana Marcos B.,
Matsuda Eduardo I.,
Nowill Alexandre E.,
Brandalise Silvia R.,
Yunes José A.
Publication year - 2007
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20953
Subject(s) - wilms' tumor , cytogenetics , myeloid leukemia , medicine , oncology , proportional hazards model , malignancy , karyotype , myeloid , clinical significance , cancer research , gene , biology , chromosome , genetics
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. Procedure 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. Pediatr Blood Cancer 2007;49:133–138. © 2006 Wiley‐Liss, Inc.

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