ISAL 2023 | Using epigenetic analysis to understand the biology of relapse in AML
Ravi Majeti, MD, PhD, Stanford University, Stanford, CA, comments on the use of chromatin biology methods to understand the processes driving relapse in patients with acute myeloid leukemia (AML). Dr Majeti explains that in patients without mutational changes between diagnosis and relapse, methods like ATAC-seq have identified the presence of epigenetic features leading to relapse. This interview took place at the 18th International Symposium on Acute Leukemias (ISAL XVIII), held in Munich, Germany.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
This year I talked about trying to understand relapsed AML using chromatin biology methods. We started with the observation that when you look at paired diagnostic and relapsed samples from the same patient, you often find a significant proportion of patients that don’t have any mutational changes, which begs the question of well then if they’re not having difference in mutations, why are they relapsing? Why are they becoming chemo-resistant? So we used epigenetic methods like ATAC-Seq to try to characterize some of these cases and really just to explore what are the evolutionary paths that cells can take from diagnosis into relapse...
This year I talked about trying to understand relapsed AML using chromatin biology methods. We started with the observation that when you look at paired diagnostic and relapsed samples from the same patient, you often find a significant proportion of patients that don’t have any mutational changes, which begs the question of well then if they’re not having difference in mutations, why are they relapsing? Why are they becoming chemo-resistant? So we used epigenetic methods like ATAC-Seq to try to characterize some of these cases and really just to explore what are the evolutionary paths that cells can take from diagnosis into relapse. And we found that there is epigenetic evolution in these cases where the mutations aren’t changing and that there can be selection of a subset of cells present at diagnosis that have the epigenetic features of relapse. But there can also be convergence of other cells into a relapsed state. So there seems to be multiple evolutionary processes going on that drive AML relapse, in this case post-chemotherapy.
Read more...
Disclosures
R.M. is on the Advisory Boards of Kodikaz Therapeutic Solutions, TenSixteen Bio, Roche, Cullgen, and 858 Therapeutics and is an inventor on a number of patents related to CD47 cancer immunotherapy licensed to Gilead Sciences. R.M. receives research support from Gilead Sciences. R.M. is a co-founder and equity holder of Pheast Therapeutics, MyeloGene, and Orbital Therapeutics.
