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SUMMARY:Origins and clonal evolution of childhood leukaemia - Tariq Enver\
 ; University College London
DTSTART:20151119T130000Z
DTEND:20151119T140000Z
UID:TALK59821@talks.cam.ac.uk
CONTACT:Neil Bennett
DESCRIPTION:Childhood acute lymphoblastic leukaemia is thought in many cas
 es to initiate in utero. The factors that influence the formation of the i
 nitiating lesions are not well understood although the nature of these gen
 etic aberrations is well documented and include in approximately a quarter
  of children the presence of the t12\;21 chromosomal translocation that fu
 ses the transcription factors Tel (ETV6) and Aml1 (RUNX1). The Tel-Aml1 fu
 sion gene produces a pre-leukaemic clone but in and of itself is insuffici
 ent to produce frank leukaemic transformation. For this\, additional mutat
 ions are required and it remains unclear what factors influence their acqu
 isition. These additional mutations tend to arise in loci that are normall
 y involved in cell fate control in the B lineage. Cell fate regulators act
  in a context dependent manner and thus understanding the nature of the ta
 rget cell or cells in which the initiating and subsequent mutations arise 
 is of importance. \n \nTo gain insight with these issues we have been expl
 oring the target genes of TEL-AML1 and associated second hits as well as d
 eveloping new foetal specific models in which to examine the biological im
 pact of TEL-AML1.\n\nLeukaemic clones appear to evolve in a branching mann
 er such that at presentation the marrow is replete with multiple variegate
 d subtypes proving a diverse substrate for selection in response to therap
 y. Beyond genetic heterogeneity\, leukaemic cells exhibit epigenetic heter
 ogeneity in respect of their immunophenotypes and functional properties in
 cluding cell cycle status and niche residence.\n\nOverall\, our studies su
 ggest that clonal selection in leukaemia results from the combined influen
 ce of genetic and epigenetic variations.\n
LOCATION:CRUK CI Lecture Theatre
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