Infants and leukemia: understanding the mechanisms behind leukemogenesis in early life

Acute leukemia in infancy, i.e. children aged 0-12 months, is characterized by KMT2A-gene rearrangements (KMT2A-r), and a very poor outcome. The biological reason for this poor outcome is not known.

My hypothesis is that that the poor outcome is connected to genomic alterations, to an intrinsic resistance, or to an age-dependent difference in the composition of normal and malignant cells in the bone marrow.

In the first project, KMT2A-r acute leukemia samples are studied at the cellular level to reveal mechanisms of therapy resistance alongside with chemotherapy modelling in PDX-models.

In the second project, KMT2A-r acute leukemia samples from infancy to adulthood are studied to uncover the molecular basis of leukemia across age groups and key findings are translated into improved clinical diagnostics and follow-up.

In the third project, genetic changes are functionally studied to delineate mechanisms underlying leukemia development including lineage fate, how treatment affects the evolution of genetically distinct clones and mechanisms of resistance. This project will be performed by myself, a PhD student, two post-docs, a research engineer, and a senior researcher.

The overall goal of this proposal is to improve our biological understanding of infant leukemia development, progression, and relapse and thereby impact how it is diagnosed and treated in the future.