Induced myeloid differentiation of K562 cells with downregulation of erythroid and megakaryocytic transcription factors: a novel experimental model for hemopoietic lineage restriction.
The human erythroleukemia cell line K562 can be induced to differentiate along the erythroid and megakaryocytic lineages. Here we demonstrate that hexamethylene bisacetamide (HMBA) induced K562 cells to differentiate along a third pathway. This was accompanied by downregulation of two transcription factors normally expressed in erythroid, mast and megakaryocyte lineages. Northern analysis demonstrated coordinate downregulation of alpha globin and gamma globin in addition to the two lineage-restricted transcription factors, SCL and GATA-1. Proliferation of the K562 cells was also suppressed. Clonal assay showed that the suppression was irreversible and appeared analogous to the commitment of murine erythroleukemia (MEL) cells to terminal differentiation. In contrast to MEL cells, however, K562 cells acquired a macrophage-like morphology and exhibited a complete failure to generate benzidine-positive cells. Electron microscopy revealed a marked increase in granules resembling those specific for eosinophils. Surface marker analysis showed that HMBA-induced cells expressed reduced levels of glycophorin A, CD5, CD7 and CD11b. No upregulation of megakaryocyte or lymphoid markers occurred. Thus the response of K562 cells to HMBA may provide a useful experimental system for studying the molecular mechanisms responsible for downmodulation of lineage-restricted transcription factors during hemopoietic lineage commitment.
Green
A R
AR
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Rockman
S
S
DeLuca
E
E
Begley
C G
CG
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology*; D006021:Glycophorins / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000954:Antigens, Surface; D006021:Glycophorins; D014157:Transcription Factors; C014026:hexamethylene bisacetamide