Establishment of a High-risk MDS/AML Cell Line YCU-AML1 and its Xenograft Model Harboring t(3;3) and Monosomy 7. Issue 5 (17th October 2020)

• Record Type: Journal Article
• 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
• Is Part Of: HemaSphere. Volume 4:Issue 5(2020)
• Page Start: e469
• Publication Date: 2020-10-17
• Subjects: Hematology -- Periodicals; 616.15005
• DOI: 10.1097/HS9.0000000000000469
• Languages: English
• ISSNs: 2572-9241

Abstract

Abstract : 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.