Most importantly, pharmacological inhibition of FOXO1 showed antileukemia activity on several primary, patient-derived, pediatric ALL xenografts with effective leukemia reduction in the hematopoietic, lymphoid, and central nervous system organ compartments, ultimately leading to prolonged survival without leukemia reoccurrence in a preclinical in vivo model of BCP-ALL.
ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions.
All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.
Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is usually initiated in utero and is thought to progress to overt leukemia under the influence of delayed exposure to a common infection.
Clustering approximately 90% of DPB1 alleles into DPB69E (DP2, 6, 8) and DPB69K (DP1, 3, 4) supertypes revealed that DP2 and DP8 are associated with BCP ALL, but DP6 is also associated with non-BCPleukaemia.
These data confirm that stCD40L exposure can activate the antigen-presenting cell (APC) capacity of BCP-ALL cells cultured on HBMS and that ELISPOT assay can be used to measure the frequency of leukemia-reactive autologous T cells in the BM of ALL patients even after short-term culture with stCD40L-stimulated ALL cells.
Comparative phenotype mapping thus allows one to distinguish between normal and leukemic cells, and we show that it may enable rapid, specific, and quantitative detection of residual/resurgent leukemia in BCP-ALL.
Only immature TCRdelta rearrangements were detected in BCP ALL (59%), whereas no rearrangement was found in the remaining BCPleukaemias, thus confirming the exclusive presence of immature TCRdelta rearrangements in B-lineage cells.