Pediatrics & Therapeutics
Open Access
ISSN: 2161-0665
ISSN: 2161-0665
Irmela Jeremias
Ludwig Maximilian University of Munich, Germany
Posters & Accepted Abstracts: Pediat Therapeut
While first line poly-chemotherapy substantially reduces tumor burden in most children with acute leukemia, a subgroup of children retain residual tumor cells in a disease stage called minimal residual disease (MRD). Despite low tumor burden, MRD represents a major threat as it consists of treatment resistant cells which might induce disease relapse with inferior prognosis. Novel treatment options are urgently required to treat children with acute leukemia at MRD. We aimed at the preclinical testing novel treatment options for MRD. Towards this aim, we established the individualized mouse model of acute leukemias and transplanted primary tumor cells from children with either Acute Lymphoblastic Leukemia (ALL) or Acute Myloid Leukemia (AML) into severely immunocompromised mice and generated patient-derived xenograft cells thereof. Using lenti-viral transduction, we molecularly marked patient-derived xenograft cells with luciferase allowing highly sensitive and reliable bioluminescence in vivo imaging in single mice over time. Imaging allowed establishing a mouse model of MRD using conventional poly-chemotherapy consisting of an anthracycline combined with Cytarabine in AML and a 3 drug poly-chemotherapy for ALL. Using enrichment strategies based on the expression of additional trans-genes, we re-isolated MRD cells from mice and performed single cell RNA sequencing to characterize the cells. We performed second line treatment starting at the disease stage of MRD. Our model allows characterizing MRD cells in more detail and testing novel treatment options to remove MRD cells in order to prevent disease relapse and to improve the prognosis of children with acute leukemias.