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Pax5 restoration in a mouse model of B progenitor acute lymphoblastic leukemia

ABSTRACT: Hypomorphic mutations of PAX5 occur in one third of B-progenitor acute lymphoblastic leukemias (B-ALLs), however their functional consequences remain undefined. Here we employ advanced transgenic RNAi in mice to suppress endogenous Pax5 expression in the hematopoietic compartment in vivo, which co-operates with activated STAT5 to induce B-ALL. In this model, restoring endogenous Pax5 expression in established B-ALL induces transcriptional and immunophenotypic changes reminiscent of normal B cell differentiation, disabling leukemia-initiating capacity and ultimately causing leukemia clearance. Comparison of leukemias harvested from triplicate untreated mice versus triplicate Dox-treated (3 days) mice

ORGANISM(S): Mus musculus

SUBMITTER: Gordon Smyth

PROVIDER: E-GEOD-52870 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia.

Liu Grace J GJ Cimmino Luisa L Jude Julian G JG Hu Yifang Y Witkowski Matthew T MT McKenzie Mark D MD Kartal-Kaess Mutlu M Best Sarah A SA Tuohey Laura L Liao Yang Y Shi Wei W Mullighan Charles G CG Farrar Michael A MA Nutt Stephen L SL Smyth Gordon K GK Zuber Johannes J Dickins Ross A RA

Genes & development 20140601 12

Loss-of-function mutations in hematopoietic transcription factors including PAX5 occur in most cases of B-progenitor acute lymphoblastic leukemia (B-ALL), a disease characterized by the accumulation of undifferentiated lymphoblasts. Although PAX5 mutation is a critical driver of B-ALL development in mice and humans, it remains unclear how its loss contributes to leukemogenesis and whether ongoing PAX5 deficiency is required for B-ALL maintenance. Here we used transgenic RNAi to reversibly suppre ...[more]

PMID: 24939936

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