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 MLL–AFF1 (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).