Developmental lymphopoiesis and leukemia

How do hematopoietic stem cells (HSC) differentiate into mature blood cells? Knowledge of how lineage commitment occurs during normal haematopoiesis is important if we are to understand underlying events that lead to leukaemia. The route to produce mature blood cells can be thought of as a hierarchical tree, with rare HSCs at the top, cells that give rise to all other cells and progenitors of the blood system and that can also self renew. Lineage commitment has been extensively studied in the adult mouse system, but less is known about the process during development. Understanding the process of lineage commitment during development and how it differs from the adult system is important since several mutations leading to childhood acute lymphoblastic leukaemia (ALL) are known to arise already in utero.
Acute Lymphoblastic Leukemia (ALL) is one of the most common cancers in children. While this type of malignancy is found in both children and adults, childhood (c) B-ALL differs from the disease in adults with higher incidence, better prognosis but also a specific mutational spectrum. These facts suggest differences in the underlying biology and in the initiation of the disease between adults and children. Many of the initiating mutations in cALL have been shown to occur already during fetal life. The targeted cells form a pre-leukemic clone, pre-disposed to develop leukemia when encountering additional mutations. How the leukemia process initiates is poorly understood and cALL offers a unique possibility to study this since many of the initiating mutations are known. The main focus of the lab is to understand how the leukemia starts: the origin of the pre-leukemic clone and the molecular pathways which regulate the initiation of the disease.

Akut Lymfatisk Leukemi (ALL) är en av de vanligaste cancerformerna hos barn. Oftast insjuknar barnet med cancer i B cellerna (B-ALL), som är en del i vårt specifika immunförsvar. I jämförelse med barn drabbas få vuxna av ALL, och incidensen är således paradoxalt nog högst under barndomen. En obesvarad fråga inom cancer generellt är hur sjukdomen startar. ALL hos barn ger unika möjligheter att studera detta då man ofta vet vilken typ av mutation som kommer först. Detta första steg har i många fall hänt redan under fosterlivet. Det innebär att barnet kan födas med ett förstadium till leukemi. För att leukemi ska uppstå krävs dock flera mutationer.
Vi vill förstå detta första steg i leukemiutvecklingen. Hur börjar sjukdomen? I vilken cell? Och hur förändras den cellen så att det utvecklas ett förstadium till leukemi? Genom ökad förståelse och kunskap om vad som händer i det initiala steget av sjukdomen hoppas vi att man i framtiden kan förbättra behandlingen för de barn som drabbas.