ICML 2023 | Results from single-cell RNA sequencing analysis of hairy cell leukemia

So classic hairy cell leukemia has always been thought of as a biologically quite homogeneous disease, with the BRAF V600E mutation being present in virtually all patients having it. But treatment responses to standard therapies have been quite different between individual patients. And so we have hypothesized that actually the disease may not be as biologically homogeneous as the data so far would have suggested. And so what we actually did, we obtained bone marrow aspirate from either HCL patients with very short-term remissions after standard treatment or with very long-term remission after standard treatment. And then we did single-cell RNA sequencing to compare patients with these short-term remissions and the long-term remissions. And actually, of course, we did not find major differences at the time of diagnosis. But if we then look at the follow-up of the short-term responders, we actually see kind of an evolution from diagnosis to first relapse and second relapse. And from my point of perspective, the actually most interesting thing is that this evolution is not actually being developed through new kinds of pathway activities and developing at first or second relapse, but that distinct subclusters responsible for the relapses are actually present already at the time of diagnosis. And so this is actually suggesting that our first strategy treatments are not efficient enough. So we have to really focus on improving our first treatment approaches.