Apoptosis deficiency defines prognostic subgroups and therapy resistance in a xenograft model of pediatric BCP-ALL

• Published in: Klinische Pädiatrie
• Main Authors: Queudeville, M, Eckhoff, SM, Debatin, KM, Meyer, LH
• Format: Conference Proceeding
• Language: English
• Published: 11.05.2009
• ISSN: 0300-8630; 1439-3824
• DOI: 10.1055/s-0029-1222672

We previously demonstrated that intact cytochrome c related activation of caspases in pediatric acute leukemia is only found in patients with favorable outcome. In a NOD/SCID/huALL model rapid engraftment (short time to leukemia, TTLshort) determines poor patient outcome. In xenograft leukemia samples intact apoptosis signaling was only found in the TTLlong group, whereas it was absent in TTLshort. In addition, a significant positive correlation of TTL and cytochrome c release indicated prolonged leukemia engraftment to be due to proficient apoptosis signaling. Leukemia bearing mice were treated according to induction therapy regimens. Recipients carrying a TTLshort leukemia showed an inferior survival after treatment than those transplanted with a TTLlong leukemia. Furthermore, a significant positive correlation of posttreatment time to reoccurrence of leukemia in the mice and cytochrome c release was found, indicating that proficient apoptosis signaling is necessary for effective therapy. Our results point to deficient apoptosis signaling as an important feature determining not only leukemia growth but also therapy resistance and consequently poor patient outcome.