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• W2984311755 abstract "Abstract Immortalized cell lines are useful for deciphering the pathogenesis of acute leukemia and developing novel therapeutic agents against this malignancy. In this study, a new human myeloid leukemia cell line YBT‐5 was established. After more than 1‐year cultivation from the bone marrow of a patient with acute monocytic leukemia, YBT cell line was established. Then a subclone, YBT‐5, was isolated from YBT using single cell sorting. Morphological and cytogenetical characterizations of the YBT‐5 cell line were determined by cytochemical staining, flow cytometry analysis, and karyotype analysis. Molecular features were identified by transcriptomic analysis and reverse transcription–polymerase chain reaction. To establish a tumor model, 5 × 10 6 YBT‐5 cells were injected subcutaneously in nonobese diabetic/severe combined immune‐deficiency (NOD/SCID) mice. DOT1L has been proposed as a potential therapeutic target for KMT2A‐related leukemia; therefore, to explore the potential application of this new cell line, its sensitivity to a specific DOT1L inhibitor, EPZ004777 was measured ex vivo. The growth of YBT‐5 does not depend on granulocyte‐macrophage colony‐stimulating factor. Cytochemical staining showed that α‐naphthyl acetate esterase staining was positive and partially inhibited by sodium fluoride, while peroxidase staining was negative. Flow cytometry analysis of YBT‐5 cells showed positive myeloid and monocytic markers. Karyotype analysis of YBT‐5 showed 48,XY,+8,+8. The breakpoints between KMT2A exon 10 and exon 11 (KMT2A exon 10/11) and MLLT3 exon 5 and exon 6 (MLLT3 exon 5/6) were identified, which was different from all known breakpoint locations, and a novel fusion transcript KMT2A exon 10/MLLT3 exon 6 was formed. A tumor model was established successfully in NOD/SCID mice. EPZ004777 could inhibit the proliferation and induce the differentiation of YBT‐5 cells. Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A‐associated leukemia." @default.
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• W2984311755 date "2019-11-11" @default.
• W2984311755 modified "2023-10-16" @default.
• W2984311755 title "Establishment and characterization of a DOT1L inhibitor‐sensitive human acute monocytic leukemia cell line YBT‐5 with a novel KMT2A‐MLLT3 fusion" @default.
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• W2984311755 doi "https://doi.org/10.1002/hon.2686" @default.
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