HIMEG-1, A CELL-LINE DERIVED FROM A CML PATIENT, IS CAPABLE OF MONOCYTIC AND MEGAKARYOCYTIC DIFFERENTIATION

We have characterized HIMeg-1, a subclone of the promega-karyoblastic cell line HIMeg, in terms of its capability of proliferation and differentiation when it is exposed to various agents. We observed that phorbol 12-myristate l3-acetate (PMA) arrested HIMeg-1 growth and induced expression of monocytic surface antigens CD11c and CD14, but not the megakaryocytic surface antigen CD41a. In addition, PMA treatment of HIMeg-1 led to rapid activation of mRNA expression of egr-1, a transcription factor involved in regulating differentiation of hematopoietic progenitor cells. On the other hand, treatment of HIMeg-1 with the activated periphera blood lymphocyte-conditioned medium (PBL-CM) resulted in greatly enhanced incorporation of H-3-thymidine into newly synthesized DNA. This enhanced H-3-thymidine incorporation appears to be specific to HIMeg-1 since the same concentrations of PBL-CM had little effect on the growth of the megakaryoblastic leukemia cell line SAM-1. The PBL-CM-induced DNA synthesis in HIMeg-1 was associated with activation of CD41a and CD41b surface antigen expression and down-regulation of expression of the erythroid marker glycophorin A and the early myeloid surface antigen CD33. HIMeg-1 capable of responding differentially to PMA and PBL-CM by changing its growth rate as well as its differentiation patterns will provide an ideal model to study the underlying mechanism regulating lineage restriction of hematopoietic progenitor cells.