Funded Research

Functional Characterization of Rare Congenital Variation in Infantile Leukemia
Principal Investigator(s):
  • McDonnell Pediatric Cancer Center
Award Mechanism:
Interdisciplinary Research Initiative
Project Period:
2/1/2014 - 1/31/2018
Total Amount:

Infant leukemia (IL) remains the deadliest of all pediatric leukemias, with a survival rate of less than 50%. Dr. Druley found that IL patients are born with a significant enrichment of rare and damaging genetic variants in leukemia-associated genes. Every infant with acute myeloid leukemia (AML) inherited damaging MLL3 gene variants from each parent, suggesting that, in a specific genomic context, infant AML requires dysfunction of MLL3.


•     Sequence all genes from non-cancer DNA of 150 IL patients and their parent(s)

•     Use IL patient-derived non-cancer stem cells to a) revert variant MLL3 alleles to wild-type in myeloid precursors (i.e., immature blood cells) and b) characterize the leukemogenic potential of patient-derived and engineered myeloid cells compared to controls

•     Characterize developmental toxicity following chemotherapy exposure to patient-derived and engineered cell lines via DNA breakage analysis, cell growth analysis, human cellular transformation and embryonic stem cell assays

Potential impact:  The use of genomics as a discovery tool for IL could lead to new insights into how inherited genetic variation influences complex disease. Moreover, this research could enable testing of novel therapeutic agents and lead to new strategies for engineering blood stem cells that could be transplanted into IL patients, ultimately improving clinical outcomes.