PML-RAR expression induces a preleukemic state.

(A) Differentiation marker analysis of bone marrow cells from recipient mice reconstituted with uninfected (Control), GFP-only (PINCO), and PML-RAR–expressing lin⁻ cells (PML-RAR). Four mice per group were analyzed 90 days after reconstitution. In the case of PINCO, the data are presented for both GFP⁺ and GFP⁻cells. Peripheral blood and spleen cell analysis gave comparable results (data not shown). In addition to MAC1, we analyzed the following markers: GR1, CD34, SCA1, TER119, and CD3 with comparable results (data not shown). (B) Lin⁻ cells were prepared from recipient mice reconstituted with PML-RAR–expressing cells, 90 days after lethal irradiation. For DNA-PCR analysis, primers specific for human PML-RAR cDNA were used to amplify DNA extracted from colonies derived from methylcellulose plating. Lane 1, negative control; lane 2, positive control. Lanes 3 to 8, 6 colonies from one representative PML-RAR reconstituted mouse, used in the analysis of differentiation markers shown in panel A. (C) In vitro differentiation analysis (MAC1) of pooled colonies derived as in panel B.