484
Views
13
CrossRef citations to date
0
Altmetric
Research Article

Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil

, , , , , & show all
Pages 1501-1509 | Received 10 Jul 2013, Accepted 16 Sep 2013, Published online: 06 Feb 2014
 

Abstract

We analyzed mutations in four genes (FLT3, KRAS/NRAS and PTPN11) that might disrupt the RAS/mitogen activated protein kinase (MAPKinase) signaling pathway, to evaluate their prognostic value in children younger than 16 years old with B-cell precursor acute lymphoblastic leukemia (Bcp-ALL). The overall survival (OS) was determined with the Kaplan–Meier method. MAPKinase genes were mutated in 25.4% and 20.1% of childhood and infant Bcp-ALL, respectively. Children with hyperdiploidy were more prone to harboring a MAPKinase gene mutation (odds ratio [OR] 3.18; 95% confidence interval [CI] 1.07–9.49). The mean OS of all cases was 54.0 months. FLT3 and PTPN11 mutations had no impact on OS. K/NRAS mutations were strongly associated with MLLAFF1 (OR 5.78; 95% CI 1.00–33.24), and conferred poorer OS (p = 0.034) in univariate analysis.

Acknowledgements

The authors would like to thank the children and parents who agreed to participate in the study. We thank the physicians and biologists from the Brazilian Collaborative Study Group of Infant Leukemia included in this study (see Appendix). We also thank Dr. Luiz Claudio Santos Thuler for remarkable advice related to the statistical analysis and Dr. Claus Meyer for critical comments on the PTPN11 sequencing analysis.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This investigation was supported by the Instituto Nacional de Câncer-Fundação Ary Frauzino, Brazilian National Research Council (CNPq #573806/2008-0) and FAPERJ (#E-26/170.026/2008, #E-26/110.509/2010, and #E-26/110.823/2012). M.E. has been supported by INCA-RJ, Brazilian Ministry of Health through the Institutional Development Program Scholarship. M.S.P.O. has been supported by a CNPq research scholarship (#309091/2007).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,065.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.