We uncovered upregulated stem cell program in leukaemic lymphoblasts of patients with IKZF1 alterations by analyzing the archived gene-expression profiling datasets. We then used a frequent IKZF1 deletion, IK6, as a model via transduction into human primitive haematopoietic cells, followed by xenotransplantation in mice. Immunophenotypically defined stem, pro-B, and immature/mature (IM/M)-B cells were collected from primary recipients for functional assay and transcriptome profiling. Successful reconstitution in secondary recipient mice revealed the stemness of IK6+ pro-B and IM/M-B cells. Upregulated stemness and malignancy programs in IK6+ cells confirmed IK6 effects. Interestingly, these programs corresponded to distinct canonical pathways. Remarkably, the pathway profile mapped in the modelled cells well mirrored that in patients leukaemic cells; therefore, our study provides a seminal insight into the cancerous reprogramming of somatic cells. SOURCE: ruoyan Li (ruoyan_li@pku.edu.cn) -  Peking University

Pluto Bioinformatics

GSE112124: Leukaemic alteration of IKZF1 primes stemness and malignancy programs in human lymphocytes