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

• Published in: HemaSphere 2020-10, Vol.4 (5), p.e469-n/a
• Main Authors: Kunimoto, Hiroyoshi, Fukuchi, Yumi, Murakami, Koichi, Ikeda, Junji, Teranaka, Hiroshi, Kato, Ikuma, Miyazaki, Takuya, Enaka, Makiko, Mitsuhashi, Takayuki, Yamazaki, Etsuko, Kameyama, Kaori, Murata, Mitsuru, Okamoto, Shinichiro, Nakajima, Hideaki
• Format: Article
• Language: English
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/HS9.0000000000000469

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.