Aino-Maija Leppä: Exploring intra-tumor heterogeneity in complex karyotype AML
Aino-Maija Leppä, Postdoctoral Fellow at DKFZ German Cancer Research Center, shared on X:
“Extremely proud to see my PhD project exploring intra-tumor heterogeneity in complex karyotype AML finally out in Nature Genetics.
They say that 10,000 hours make you an expert, so I guess after more than five years of work I’m half-way there.
We integrated single-cell resolution structural variants, nucleosome occupancy, gene expression and surface proteins to study subclonal growth patterns in complex karyotype AML patient samples.
For example, in one patient the subclone driving relapse had a seismic amplification, upregulated DNA damage response and it also engrafted in mice. We could even see cell-to-cell differences in the copy-number states of the seismic amplification!
In another patient with paired pre- and post-treatment samples, two distinct subclones persisted post venetoclax-based treatment. Both had subclone-specific mechanisms to further resistance: a shift toward MEP-like cells and NF1 loss. Go and read more about the other cases!
I’m very thankful to everyone involved in the study! The project would not have been possible without my co-firsts, Karen Grimes and Hyobin Jeong and co-lasts Andreas Trumpp, Jan Korbel and Ashley D Sanders.”
Authors: Aino-Maija Leppä, Karen Grimes, Hyobin Jeong, Frank Y. Huang, Alvaro Andrades, Alexander Waclawiczek, Tobias Boch, Anna Jauch, Simon Renders, Patrick Stelmach, Carsten Müller-Tidow, Darja Karpova, Markus Sohn, Florian Grünschläger, Patrick Hasenfeld, Eva Benito Garagorri, Vera Thiel, Anna Dolnik, Bernardo Rodriguez-Martin, Lars Bullinger, Krzysztof Mrózek, Ann-Kathrin Eisfeld, Alwin Krämer, Ashley D. Sanders, Jan O. Korbel and Andreas Trumpp
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