Loss of ISWI ATPase SMARCA5 (SNF2H) in Acute Myeloid Leukemia Cells Inhibits Proliferation and Chromatid Cohesion

• DOI: 10.3390/ijms21062073
• Publication Date: 2020-03-19T07:54:14Z
• Authors: Tomas Zikmund; Helena Paszekova; Juraj Kokavec; Paul Kerbs; Shefali Thakur; Tereza Turkova; Petra Tauchmanova; Philipp A. Greif; Tomas Stopka
• Keywords: Adenosine Triphosphatases; Male; 0301 basic medicine; Chromosomal Proteins, Non-Histone; leukemia; therapeutic target; Chromatids; Article; Neoplasm Proteins; Gene Knockout Techniques; Leukemia, Myeloid, Acute; 03 medical and health sciences; AML; SMARCA5; CRISPR; Cell Line, Tumor; Humans; Female; SNF2H; K562 Cells; Cell Proliferation

ISWI chromatin remodeling ATPase SMARCA5 (SNF2H) is a well-known factor for its role in regulation of DNA access via nucleosome sliding and assembly. transcriptionally inhibits the myeloid master regulator PU.1. Upregulation was previously observed CD34+ hematopoietic progenitors acute leukemia (AML) patients. Since high levels are necessary intensive cell proliferation cycle progression developing stem progenitor cells mice, we reasoned that removal enzymatic activity could affect cycling or undifferentiated state leukemic progenitor-like clones. Indeed, CRISPR/cas9-mediated knockout AML lines (S5KO) inhibited progression. We also deletion induced karyorrhexis nuclear budding as well increased ploidy, indicating mitotic division cells. The cytogenetic analysis S5KO revealed premature chromatid separation. conclude deleting blocks cohesion.