Just out in @BloodJournal – our study exploring the origin of late relapses in T-ALL. Here's a short thread with our unexpected results!.

Beautiful work by @minimolecule to dissect oncogene activation in T-ALL.

RT @BaylonK: Liza is a dedicated paediatrician who lost her husband (another well respected and loved neonatologist) to COVID. Please read….

And definitely not the end – several projects ongoing and hopefully a big story to share later this year! Update on new job coming soon! 👀.

Huge thanks to my supervisor @Marcrmansour for endless patience and support, and the many members of the lab. Particular shout-outs to the amazing scientists willing to help an incompetent medic and who made it all so enjoyable! @minimolecule @VLlombs Joana Costa @there_leon.

Time to bid a fond farewell to @uclcancer having completed my @CRUKresearch Clinician Scientist Fellowship. It’s been an incredible 6 years working on some great projects that I hope have progressed our knowledge of childhood leukaemia.

Really important work out in @NatureMedicine demonstrating the power of whole genome sequencing to improve treatment for children with cancer. Led by @DrJackBartram & Sam Behjati @GreatOrmondSt @sangerinstitute @addenbrookes.

RT @DrJackBartram: Thank you to all the patients and families involved in this pivotal study which proves the real time, real world evidenc….

Massive cuts in clinician scientist fellowships over the last few years and an overlong application process that engenders attrition suggests this is less of a CRUK priority than this article would have you believe.

RT @MAF_Dawson: I love this 👇🏾- great work from @drdavidoconnor @Marcrmansour.

Huge thanks to everyone involved including @minimolecule @DrJackBartram @JavierHerrero7 @isidrolauscher @Marcrmansour @uclcancer @DBC_ICH @emblebi and funders including @CRUKresearch @GOSHCharity .And particular thanks to the patients and families who donate samples for research.

To complete the story we were lucky to be able to go back to the stored neonatal blood spot sample for one patient, showing the same LMO2 non-coding lesion was present at birth confirming that it had occurred in utero – the first time this has been shown for a non-coding lesion.

Since the non-coding lesion occurs in both leukaemias, we can be certain it is acting as the initiating driver (ie. the first hit) in a preleukaemic cell. Whilst the first leukaemia is treated successfully, the preleukaemic clone evades chemo and evolves into a second leukaemia

Nope, not that simple! Unexpectedly, four of the cases had identical non-coding lesions at diagnosis and relapse – 3 driving LMO2 and 1 driving TAL1. All these mutations have been described by us and others previously, but never linked to relapse

With access to newer tech, we wanted to re-examine this hypothesis so did WGS in 7 cases with discordant TCR rearrangements at diagnosis/relapse. In keeping with hypothesis, not a single coding variant was shared between diagnosis and relapse. So two unrelated malignancies right?.

T-ALL is highly aggressive – when it relapses, it is usually early. But it’s been known for a while that some rare cases will relapse years later with previous work suggesting the relapse is actually a second de novo leukaemia – if true, this has important clinical implications.

RT @rail_guns: This isn't just good leaflet copy, this is why politics matters and different parties aren't all "just the same". Here's a….

RT @NatureMedicine: Academic clinician–scientists risk becoming an endangered species. World View from @StephenORahilly @Cambridge_Uni. ht….

Although CNS status still impacts on outcome, this is not overcome through the use of CRT - it simply increases toxicity. Alternative approaches are needed (3/3)

This is something of a companion piece to the recent COG paper showing CRT had little benefit in children with T-ALL and CNS-1 or CNS-2 at diagnosis. Our data suggest same is true even in those with CNS-3 at diagnosis. (2/3).