I am studying the E1910 cohort in ASH, this is about [??] clinical trial and my study tried to focus on the genomic data of the case and also compared to previous studies I will include Ph+ cases. So I tried to analyse all the genomic data in the E1910 case and this may be bigger data for [??] genomic analysis.

What was the study design?

By analysing the genomic data we tried to answer some questions, including that [??] randomised in clinical trials. We can separate the patients to subgroups like some cases that have achieved MRD negative status, some are MRD positive, some are induction failure. We tried to see what genomic factors might be contributing to these three groups. We also tried to see can we identify some new groups from this data.

What were the key results?

First that we were able to see the subtype difference among these three groups, like in MRD positive and induction failure they seem to enrich more for Ph-like subtypes, including Ph-like CRLF2 and KMT2A subtypes. In the MRD negative group there are more PAX5 alterations and also TCF3-PBX1. So maybe the genomic lesions underlying this subgroup, like KMT2A alteration may be contributing to the alteration of this group.

I also identified a new subtype which is characterised by high CEBPA or CEBPB expression. We were able to find a potential mechanism to drive the high expression, maybe driven by enhancer hijacking or maybe creating some new enhancer. Especially for the cases that have a new enhancer we were able to Nanopore ATAC-seq and [??] technology to validate why they drive the high expression of CEBPA. Especially with a long Nanopore rate we were able to link the alteration to the expression in [??] and then this is super-cool actually.

We also found that blinatumomab maybe had a better outcome in some subtypes. This also won some [??] funding for future clinical trials.

What is the clinical significance of these results?

One is that we found blinatumomab can improve outcomes in some subtypes, like Ph-like CRLF2, hyperdiploid. These two subtypes, especially for Ph-like CRLF2, is similar to Ph positive cases, that is a reason, maybe it explains why blinatumomab works. While we can notify the difference in paths for TNF and especially the worst subtype, [??] so maybe next we’ll try to identify what the potential mechanism can improve treatment in [??].

How does the newly identified genomic subset differ clinically or biologically from the previously recognised ALL subtypes?

For the new subtype it’s characterised by high CEBPA and B expression which is maybe important in B-cell development. But at the moment we don’t see too much difference in expression between this group and the others. Overall survival in this group seems to be no different from others, it seems a median-risk group but since the number is small maybe in the future we may still try to find more cases to see the difference.

When identifying a new group we can combine Nanopore and other data together, helping us to find the lesions that maybe can explain this subgroup. I think that’s the most important in my opinion.