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Publication : 5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies.

First Author  Wong JC Year  2024
Journal  Leukemia Volume  38
Issue  5 Pages  1182-1186
PubMed ID  38443608 Mgi Jnum  J:352285
Mgi Id  MGI:7705809 Doi  10.1038/s41375-024-02205-x
Citation  Wong JC, et al. (2024) 5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies. Leukemia 38(5):1182-1186
abstractText  Monosomy 7 and del(7q) are among the most common and poorly understood genetic alterations in myelodysplastic neoplasms and acute myeloid leukemia. Chromosome band 7q22 is a minimally deleted segment in myeloid malignancies with a del(7q). However, the rarity of "second hit" mutations supports the idea that del(7q22) represents a contiguous gene syndrome. We generated mice harboring a 1.5 Mb germline deletion of chromosome band 5G2 syntenic to human 7q22 that removes Cux1 and 27 additional genes. Hematopoiesis is perturbed in 5G2(+/del) mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with Kras(G12D), Nras(G12D), or the MOL4070LTR retrovirus in leukemogenesis. 5G2(+/del) mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).
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