Chromatin remodeling gene SMARCA5 is dysregulated in primitive hematopoietic cells of acute leukemia.
We identified a subset of genes involved in chromatin remodeling whose mRNA expression changes in differentiating mouse erythroleukemia (MEL) cells. We furthermore tested their mRNA expression patterns in normal and malignant CD34+ bone marrow cells. SMARCA5, imitation switch gene homologue, was rapidly silenced during in vitro erythroid differentiation of MEL cells whereas it was up-regulated in CD34+ hematopoietic progenitors of acute myeloid leukemia (AML) patients. Moreover, SMARCA5 mRNA levels decreased in AML CD34+ progenitors after the patients achieved complete hematologic remission. We detected high levels of SMARCA5 mRNA in murine bone marrow and spleen and monitored its expression in these hematopoietic tissues during accelerated hematopoiesis following hemolytic anemia induced by phenylhydrazine. SMARCA5 expression levels decreased after the onset of accelerated erythropoiesis. Our data suggest that both in vitro and in vivo induction of differentiation is followed by down-regulation of SMARCA5 expression. In CD34+ AML progenitors over-expression of SMARCA5 may thus dysregulate the genetic program required for normal differentiation.
Institute of Hematology and Blood Transfusion and Department of Pathophysiology, First Medical Faculty, Charles University, Prague, Czech Republic.
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Stopka
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Zakova
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Fuchs
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Kubrova
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Blafkova
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Jelinek
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Necas
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Zivny
D000208:Acute Disease; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010659:Phenylhydrazines / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013382:Subtraction Technique; D014407:Tumor Cells, Cultured
D002843:Chromatin; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D010659:Phenylhydrazines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C030299:phenylhydrazine; D004250:DNA Topoisomerases, Type II