Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia

Churchman et al (2015) Cancer Cell                                        

Link to abstract: http://www.cell.com/cancer-cell/abstract/S1535-6108(15)00268-8

Multiple methods were used in mouse models and human-derived cell cultures to reach the following findings:

  • IKZF1 and Arf mutations confer lymphoid stem cell lineage in Ph+ cells. Ph+ cells in the absence of IKZF1 mutations are much more likely to develop into a myeloid phenotype.
  • IKZF1 mutations increase the adhesiveness of leukemia cells and this increases their ability to adhere to the bone marrow niche.
  • Mice with Ph+/IKZF1+/- or combined with other Ikaros-related downstream mutations had a poorer survival with dasatinib therapy than Ph+ with wild type IKZF1
  • Retinoids improved the response to dasatinib in in vitro assays as well as in the mouse model and was better than a combination of dasatinib with conventional chemotherapy (in mice with Ph+ and an Ikaros mutation).