Startseite Kongressberichte 2020 Virtual Edition of the 25th Annual Congress of the European Hematology Association Oral Sessions Acute Leukemia ALL: ALL:

ALL Biology

 
Laura Hinze, Sabine Schreek, James Degar, et al.
 
The authors of the abstract conclude: 
Inducible phase separation of GSK3α represents a previously unrecognized response to amino acid starvation, and correlates with asparaginase resistance in human PDXs. These results provide a compelling rationale for testing GSK3α body formation as a biomarker for asparaginase resistance in acute leukemias.————————————————————————————————————————————————————————
 
 
Kirsten Canté-Barrett, Valentina Cordo, Marloes Nulle, et al.
 
The authors of the abstract conclude: 
We provide first evidence that MEF2C acts as a bona fide oncogene that drives biphenotypic leukemia in mice. This model therefore recapitulates human ETP-ALL that also express B cell lineage markers in addition to T/myeloid markers and represents human mixed phenotype acute leukemia (MPAL). Our results point to SIK kinase inhibitors as a therapeutic option in ETP-ALL that promotes differentiation by inhibiting MEF2C function.
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Guillaume Andrieu, Milena Kohn, Charlotte Smith, et al.
 
The authors of the abstract conclude: 
PRC2-altered T-ALL define a unique phenotypic, transcriptomic, molecular and epigenetic profile. PRC2 loss-of-function induces a BET protein-dependent transcriptomic program that can be targeted to counter T-ALL progression.
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Siobhan Rice, Nicholas Fordham, Nicholas T Crump, et a.
 
The authors of the abstract conclude: 
Here we describe a CRISPR-Cas9-induced chromosomal translocation model of t(4;11) pro-B ALL that faithfully recapitulates iALL-like disease for the first time. This is consistent with the crucial importance of the fetal cell context for initiation of iALL by MLL-AF4. Using this model, we have shown that MLL-AF4 binding causes marked enrichment of H3K79me2 at target loci, suggesting that recruitment of DOT1L is an important function of MLL-AF4 during leukaemic transformation. We identify PAF1 as the “missing link” by which MLL-AF4 can recruit DOT1L.
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Paulina Richter-Pechanska, Joachim Kunz, Tobias Raush, et al.
 
The authors of the abstract conclude: 
T-ALLs that develop into type 2 relapses are more heterogeneous at the time of the initial disease with several coexisting subclones and undergo more extensive clonal and (epi)genetic remodeling on the road to relapses.  By contrast, T-ALLs that develop into type 1 relapses are more homogenous in their clonal architecture and already resemble the relapsed leukemia at the time of first diagnosis. Therefore, the propensity to develop into a type 1 relapse appears to be inherent to the original clonal and genetic composition of these leukemias.