Josep Carreras Leukaemia Research Institute B-ALL is the most common paediatric cancer and, over the years and thanks to a very effective treatment based on glucocorticoids, its 5-year survival rates have reached 85% and beyond. However, there is a B-ALL subtype, commonly found in infants (less than 1 year old), that responds very poorly to glucocorticoids and, with no other therapeutic alternative, its prognosis is dismal and survival rates still fall below 30%. The common feature of this glucocorticoid-resistant B-ALL subtype is the rearrangement of the MLL gene.
This means that a DNA fragment with this gene has moved elsewhere in the genome, in a sort of random genetic cut-and-paste. This is actually very common in cancer cells and, depending on where the fragment is pasted, there might be consequences. In most cases of B-ALL with MLL rearrangements (MLLr B-ALL), this gene fuses with another one named AF4, producing a new fusion protein (MLL-AF4) with unexpected activities.
A complex series of events The findings of the team, spearheaded by Dr. Belén López-Millán (also member of the University of Granada) and Dr. Clara Bueno, in collaboration with Dr.
Jose Luis Sardina and Dr. Biola Javierre (Josep Carreras Institute) and Dr. Juan Ramón Tejedor and Mario Fraga's team (CINN/CSIC - ISPA - IUOPA), as well as other research teams from Spain, Italy, Germany and the UK, show how the events following the MLL-AF4 fusion end up producing the characteristic glucocorticoid re.