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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE112124 | GEO | 2018/05/17

REPOSITORIES: GEO

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

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