Klin Padiatr 2010; 222 - A10
DOI: 10.1055/s-0030-1254461

Intact apoptosis signaling in pediatric ALL is associated with patient outcome, low expression of anti-apoptotic molecules and long NOD/SCID engraftment

F Seyfried 1, M Queudeville 1, SM Eckhoff 1, KM Debatin 1, LH Meyer 1
  • 1Department of Pediatrics and Adolescent Medicine, University of Ulm, Germany

We recently reported the importance of intact apoptosis signaling for treatment response in pediatric ALL and AML analyzing two key apoptogenic events, cytochrome c release and caspase-3 activation. In a NOD/SCID/huALL xenograft model we found that rapid in vivo leukemia growth (Time to leukemia (TTL) short) in mice determines poor patient outcome.

In this study we investigated apoptosis signaling and expression of apoptosis regulating molecules in ALL xenograft cells. Correlation of cytochrome c release and caspase-3 activation indicating proficient apoptosis signaling was only present in xenografts from patients with good treatment response, favorable prognosis, slow in vivo leukemia growth (TTLlong) and low expression of the anti-apoptotic molecules Mcl-1, XIAP, Bcl-2 and Livin. Patients with intact apoptosis signaling showed a superior relapse free survival in contrast to samples with apoptosis deficiency.

Thus, the propensity of leukemia cells to undergo apoptosis leads to prolonged engraftment in the NOD/SCID/huALL model, is associated with low expression of anti-apoptotic molecules and results in a favorable treatment response and superior survival of pediatric ALL patients.