University of Groningen
Unraveling clonal heterogeneity in acute myeloid leukemia
de Boer, Bauke
DOI:
10.33612/diss.113125010
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Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
de Boer, B. (2020). Unraveling clonal heterogeneity in acute myeloid leukemia. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.113125010
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Stellingen
behorende bij het proefschriftUnraveling clonal heterogeneity in Acute Myeloid Leukemia
1. Somatic mutations in hematopoietic stem/progenitor cells result in aberrant plasma
membrane protein expression, which allows us to identify and isolate genetically distinct subclones (this thesis)
2. Analyses of AML cell populations without taking clonal heterogeneity into account can
give an incomplete view if multiple subclones are present in one AML patient (this thesis)
3. Tracking clonal drift in in vitro and in vivo models is essential in order to draw the
correct conclusions (this thesis, Klco et al., 2014 Cancer Cell)
4. Leukemia-enriched plasma membrane proteins are good targets for subclone-specific
therapy and allow us to track AML subclones longitudinally (this thesis, Perna et al. 2017 Cancer Cell)
5. Different genetic mutations in AML (sub)clones impact differently on chromatin
accessibility, transcription factor occupancy and gene transcription (this thesis, Assi et
al. 2019 Nat. Gen.)
6. A human bone marrow niche in mice increases AML engraftment, better recapitulates
the AML stem cell characteristics and allows for relatively simple genetic engineering in order to study bone marrow niche interactions (this thesis, Antonelli et al., 2016 Blood, Reinish et al., 2016 Nat. Med.)
7. IL1-IL1RAP signal transduction in AML plays an important role in the inflammatory
bone marrow microenvironment whereby normal hematopoiesis is suppressed (this thesis)
8. “Cancers evolve over variable time frames (~1–50 years) and tempos and, in
any one patient, the clonal structure, genotype and phenotype shifts over time. Contemporaneously, any one cancer is, in effect, multiply different (sub-clonal) cancers occupying overlapping or distinct tissue habitats.” (Mel Greaves and Carlo C. Maley, 2012 Nature)
9. De ware optimisten zijn er niet van overtuigd dat alles goed zal gaan, maar zij zijn er wel
van overtuigd dat niet alles fout zal gaan. (Jean Dutourd)
10. “What day is it?”, asked Pooh. “It’s today,” squeaked Piglet. “My favorite day,” said
Pooh. (Alan Alexander Milne)