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Direct Lineage Reprogramming of Adult Mouse Fibroblast to Erythroid Progenitors
Published on: December 14, 2018
JAS-R, a new megakaryo-erythroid leukemic cell line that secretes erythropoietin
Tetsuaki Sekikawa1, Satsuki Iwase, Shinobu Saito
1Division of General Medicine, Aoto Hospital, Jikei University School of Medicine, Tokyo 125-8506, Japan.
Background:
The processes of leukemogenesis and differentiation of the megakaryo-erythroid lineage remain poorly understood. Leukemic cell lines derived from megakaryocytic leukemia are valuable reagents for studies on these events.
Materials And Methods:
A new cell line, JAS-R, was established from a 64-year-old patient with acute megakaryocytic leukemia (AML M7). Its characteristics were studied by morphological, immunophenotypic and molecular biological analysis.
Results:
Immunophenotyping showed that the JAS-R cells were positive for CD33, CD41 and CD61, as well as moderately to weakly positive for CD4, CD7, CD13 and glycophorin A. Chromosomal analysis revealed a composite karyotype, but no major translocation abnormalities were observed. Electron microscopy disclosed that the JAS-R cells had numerous surface blebs and some cells also had alpha-granules and demarcation membranes. The mRNAs of 4 major proteins (platelet factor 4, beta-thromboglobulin, selectin-P and thrombospondin 1) found in alpha-granules were all expressed by the JAS-R cells. In particular, expression of platelet factor 4 was high. To further characterize JAS-R cells, comparison with 4 other megakaryo-etythroid cell lines (CMK, MEG-01, K562 and KU812) was done by gene expression profiling using an oligo-DNA microarray. The results showed that JAS-R was a distinctive cell line. It was noteworthy that the JAS-R cells secreted erythropoietin and expressed erythropoietin receptor. A neutralizing antibody for erythropoietin partly inhibited the proliferation of the cells.
Conclusion:
JAS-R may be a useful cell line for investigating the differentiation and leukemogenesis of megakaryo-erythroid cells and for studying the influence of erythropoietin on these cells.
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