SUPPRESSION OF APOPTOSIS DURING CYTOKINE DEPRIVATION OF 32D CELLS IS NOT SUFFICIENT TO INDUCE COMPLETE GRANULOCYTIC DIFFERENTIATION

The role of cytokines in the control of hematopoietic cell differentia tion remains controversial. Two general models for the cytokine contro l of hematopoietic differentiation have been proposed. In the stochast ic model, cytokines provide proliferative and survival signals to the differentiating hematopoietic cell, but they do not provide specific l ineage commitment signals, In the instructive model, cytokines transmi t specific signals to multipotent hematopoietic cells, thereby directi ng lineage commitment. To distinguish between these two models with re spect to granulocyte colony-stimulating factor (G-CSF) and granulocyti c differentiation, we used the 32Dcl3 cell line, which is capable of d ifferentiating into granulocytes in response to G-CSF, 32D cells trans fected with either bcl-2 or bcl-X(L) showed prolonged survival in medi um containing no cytokine supplement, Cells surviving in these culture s developed the segmented nuclei characteristic of mature neutrophils. However, no induction of myeloperoxidase activity or increase in cath epsin G transcripts were detected. These data support a hybrid model f or the role of G-CSF in granulocytic differentiation; although some fe atures of granulocytic differentiation, namely nuclear segmentation, d o not require G-CSF and appear therefore to be preprogrammed in 32D ce lls, the complete maturation of these cells to granulocytes appears to be dependent on G-CSF. (C) 1996 by The American Society of Hematology .