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Updated: Jun 1, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
Published on: August 19, 2014
Loss of p19Arf in a Rag1(-/-) B-cell precursor population initiates acute B-lymphoblastic leukemia
Julia Hauer1, Charles Mullighan, Estelle Morillon
1Inserm U768, René Descartes University of Paris, and Necker Children's Hospital, Paris, France.
Abstract:
In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf(-/-)Rag1(-/-) mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1(+)CD19(+) precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34(+)CD19(+) population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans.
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