INDUCED MYELOID DIFFERENTIATION OF K562 CELLS WITH DOWN-REGULATION OFERYTHROID AND MEGAKARYOCYTIC TRANSCRIPTION FACTORS - A NOVEL EXPERIMENTAL-MODEL FOR HEMATOPOIETIC LINEAGE RESTRICTION

The human erythroleukemia cell line K562 can be induced to differentia te along the erythroid and megakaryocytic lineages. Here we demonstrat e that hexamethylene bisacetamide (HMBA) induced K562 cells to differe ntiate along a third pathway. This was accompanied by downregulation o f two transcription factors normally expressed in erythroid, mast and megakaryocyte lineages. Northern analysis demonstrated coordinate down regulation of alpha globin and gamma globin in addition to the two lin eage-restricted transcription factors, SCL and GATA-1. Proliferation o f the K562 cells was also suppressed. Clonal assay showed that the sup pression was irreversible and appeared analogous to the commitment of murine erythroleukemia (MEL) cells to terminal differentiation. In con trast to MEL cells, however, K562 cells acquired a macrophage-like mor phology and exhibited a complete failure to generate benzidine-positiv e cells. Electron microscopy revealed a marked increase in granules re sembling those specific for eosinophils. Surface marker analysis showe d that HMBA-induced cells expressed reduced levels of glycophorin A, C D5, CD7 and CD11b. No upregulation of megakaryocyte or lymphoid marker s occurred. Thus the response of K562 cells to HMBA may provide a usef ul experimental system for studying the molecular mechanisms responsib le for downmodulation of lineage-restricted transcription factors duri ng hemopoietic lineage commitment.