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. 2024 Nov;38(11):2479-2482.
doi: 10.1038/s41375-024-02399-0. Epub 2024 Sep 10.

Diverse mechanisms of leukemogenesis associated with PAX5 germline mutation

Laura Rachele Bettini #  1   2 , Grazia Fazio #  2   3 , Claudia Saitta  3 , Rocco Piazza  2   4 , Sonia Palamini  3 , Chiara Buracchi  3 , Stefano Rebellato  3 , Nicola Santoro  5 , Cristiano Simone  6   7 , Andrea Biondi  1   2 , Giovanni Cazzaniga  8   9
Affiliations

Diverse mechanisms of leukemogenesis associated with PAX5 germline mutation

Laura Rachele Bettini et al. Leukemia. 2024 Nov.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Characterization of germline and somatic variants in the family.
A Familial segregation of PAX5 p.Gly183AlafsTer84. The germline variant in the two siblings was demonstrated to be inherited from the father (II.6) and the grandmother (I,4) both asymptomatic carriers with no history of cancer. *: non tested. B Western blot analysis of Pax-5 expression. PAX5 expression was evaluated in CASE B (A), in the wild-type mother (B), control lymphoblastoid cell line (C); only the wild-type PAX5 protein (42 kD) was detected. C PAX5 variant allele analysis. Long read sequencing proved that the two identified variants are in trans, as shown in the image. The sequence variants are highlighted in red. Cumulative read depth is shown on top of the figure; sequence reads were aligned to the human GRCh38/hg38 reference.
Fig. 2
Fig. 2. Cytofluorimetric analysis of B cell repertoire in healthy PAX5 variant carriers.
a B cell repertoire on fresh peripheral blood mononuclear analysis showed a reduction in memory B cells IgD− CD27+ (mean ± SD of PAX5 mutated carriers vs wild-type healthy donors: 9 ± 6% vs 27% ± 11%; p = 0.07). b Dot plot of a PAX5 wild-type healthy donor compared with a PAX5 mutated carrier.
See this image and copyright information in PMC

References

    1. Wagener R, Elitzur S, Brozou T, Kubaczkova V, Bibi S, Hof J, et al. Functional damaging germline variants in ETV6, IKZF1, PAX5 and RUNX1 predisposing to B-cell precursor acute lymphoblastic leukemia. Eur J Med Genet. 2023;66:104725. - PubMed
    1. Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukemia. Nature. 2007;446:758–64. - PubMed
    1. Stasevich I, Inglott S, Austin N, Bown N, Hall G, Harrison CJ, et al. PAX5 alterations in genetically unclassified childhood precursor B-cell acute lymphoblastic leukemia. Br J Haematol. 2015;171:263–72. - PubMed
    1. Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, et al. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet. 2013;45:1226–31. - PMC - PubMed
    1. Auer F, Ruschendorf F, Gombert M, Husemann P, Ginzel S, Izraeli S, et al. Inherited susceptibility to pre B-ALL caused by germline transmission of PAX5 c.547G>A. Leukemia. 2014;28:1136–8. - PubMed

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