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Research Paper|Volume 2, Issue 12|pp 908—913

The age of the target cell affects B-cell leukaemia malignancy

Carolina Vicente-Dueñas1, Fernando Abollo-Jiménez1,4, Lucía Ruiz-Roca1, Esther Alonso-Escudero1, Rafael Jiménez2, María Begoña García Cenador3, Francisco Javier García Criado3, César Cobaleda4, Isidro Sánchez-García1
  • 1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/ Universidad de Salamanca, Campus M. de Unamuno s/n, 37007- Salamanca, Spain
  • 2Departamento de Fisiología y Farmacología, Universidad de Salamanca, Edificio Departamental, Campus M. de Unamuno s/n, 37007- Salamanca, Spain
  • 3Departamento de Cirugía, Universidad de Salamanca, Spain
  • 4Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma, Madrid, Spain
Received: December 3, 2010Accepted: December 10, 2010Published: December 11, 2010
https://doi.org/10.18632/aging.100244

Copyright: © 2010 Vicente-Dueñas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The incidence, malignancy and treatment resistance of many types of human B-cell leukaemias (B-ALL) are directly related to patient age. A major obstacle to elucidate the contribution of age to the development and evolution of leukaemias is the lack of appropriate mouse models where precise control of the timing of oncogene expression is possible. Here we present proof-of-principle experiments showing how a conditional transgenic mouse model of BCR-ABLp190-driven B-ALL offers the opportunity to test the hypothesis that the age of the leukemic cells-of-origin of B-ALL influences B-ALL malignancy. B-ALLs generated from 12- and 20-month-old progenitors gave rise to a more invasive B-ALL than the one developed from 4-month old precursors. This was evidenced by survival analysis revealing the increased malignancy of B-ALLs generated from 20 or 12-month-old transformed progenitors compared with the 4-month equivalents (median survival of 88 days versus 50.5 and 33 days, respectively). Our study shows that the age of target cells at the time of transformation affects B-ALL malignancy.