Establishment of a High-risk MDS/AML Cell Line YCU-AML1 and its Xenograft Model Harboring t(3;3) and Monosomy 7

Autor: Hiroyoshi Kunimoto, Yumi Fukuchi, Koichi Murakami, Junji Ikeda, Hiroshi Teranaka, Ikuma Kato, Takuya Miyazaki, Makiko Enaka, Takayuki Mitsuhashi, Etsuko Yamazaki, Kaori Kameyama, Mitsuru Murata, Shinichiro Okamoto, Hideaki Nakajima
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: HemaSphere, Vol 4, Iss 5, p e469 (2020)
Druh dokumentu: article
ISSN: 2572-9241
00000000
DOI: 10.1097/HS9.0000000000000469
Popis: Abstract. Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with both inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 defines an extremely aggressive myeloid cancer whose molecular pathogenesis and optimal therapeutic strategy still remain unclear. We established a new MDS/AML cell line, YCU-AML1, and its patient-derived xenograft (PDX) model from a high-risk MDS patient who later transformed into AML harboring both t(3;3)(q21;q26.2) and monosomy 7. YCU-AML1 cells propagated in co-culture system with stromal cells in granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent manner. CD34+ bone marrow cells derived from our PDX model showed high EVI1 and low GATA2 expression. Moreover, mutational profile of our MDS/AML model was consistent with recently published mutational spectrum of myeloid malignancies with inv(3)/t(3;3). These data suggest that YCU-AML1 cells and its MDS/AML model strongly mimics a high-risk human myeloid cancer with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 in terms of both clinical phenotype and molecular basis. We believe our model can be used as a feasible tool to further explore molecular pathogenesis and novel treatment strategy of high-risk MDS/AML with t(3;3)(q21;q26.2) and monosomy 7.
Databáze: Directory of Open Access Journals
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