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

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 supp...

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Bibliographic Details
Published in:Leukemia 2024-05, Vol.38 (5), p.1182-1186
Main Authors: Wong, Jasmine C, Weinfurtner, Kelley M, Westover, Tamara, Kim, Jangkyung, Lebish, Eric J, Del Pilar Alzamora, Maria, Huang, Benjamin J, Walsh, Michael, Abdelhamed, Sherif, Ma, Jing, Klco, Jeffery M, Shannon, Kevin
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Alkylation
Animals
Blood diseases
Cell cycle
Cell division
Chromosome 7
Chromosome Deletion
Chromosomes
Chromosomes, Human, Pair 7 - genetics
Competition
Cooperation
Disease Models, Animal
Gene deletion
Genes
Hematological diseases
Hematopoiesis
Hematopoietic stem cells
Hemopoiesis
Humans
Letter
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - pathology
Leukemogenesis
Malignancy
Mice
Mice, Inbred C57BL
Monosomy
Mutation
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - pathology
Neoplasms
Radiation
Segments
Stem cells
Synteny
Transplants & implants
Tumors
Citations: Items that this one cites
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Description
Summary: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 mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with Kras , Nras , or the MOL4070LTR retrovirus in leukemogenesis. 5G2 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).
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-024-02205-x