Abstract
Previously, we found that rapid leukemia engraftment (short time to leukemia, TTLshort) in the NOD/SCID/huALL (non-obese diabetic/severe combined immuno-deficiency/human acute lymphoblastic leukemia) xenograft model is indicative of early patient relapse. As earlier intact apoptosis sensitivity was predictive for good prognosis in patients, we investigated the importance of apoptosis signaling on NOD/SCID/huALL engraftment. Intact apoptosome function as reflected by cytochrome c-related activation of caspase-3 (CRAC-positivity) was strongly associated with prolonged NOD/SCID engraftment (long time to leukemia, TTLlong) of primary leukemia cells, good treatment response and superior patient survival. Conversely, deficient apoptosome function (CRAC-negativity) was associated with rapid engraftment (TTLshort) and early relapse. Moreover, an intact apoptosis signaling was associated with high transcript and protein levels of the pro-apoptotic death-associated protein kinase1 (DAPK1). Our data strongly emphasize the impact of intrinsic apoptosis sensitivity of ALL cells on the engraftment phenotype in the NOD/SCID/huALL model, and most importantly also on patient outcome.
Highlights
In a recent study we have characterized engraftment of patient acute lymphoblastic leukemia (ALL) samples transplanted onto non-obese diabetic (NOD)/severe combined immuno-deficiency (SCID) mice and identified that a short time between transplantation and onset of leukemia-related morbidity in the recipient animals is a strong prognostic factor indicative for early relapse independently of established markers
As earlier intact apoptosis sensitivity was predictive for good prognosis in patients, we investigated the importance of apoptosis signaling on NOD/SCID/huALL engraftment
Twenty-three leukemia xenografts which were established employing our NOD/SCID/huALL xenotransplant mouse model were investigated in this study
Summary
Twenty-three leukemia xenografts which were established employing our NOD/SCID/huALL xenotransplant mouse model were investigated in this study. Recipient animals were regularly examined for the onset of leukemia and killed upon disease manifestation. The presence of high leukemia infiltration was confirmed in
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
