NUP98-HOXA9 and HOXA9genetically interact with BCR-ABL to acutely transform bone marrow cells.
(A) Semiquantitative RT-PCR analysis demonstrates high levels ofHOXA9 in cells obtained from CML patients at diagnosis of myeloid blast transformation (lanes 1, 2, 4; AML) and low levels in cells from patients in the accelerated phase (AP; pre-AML) of their disease (lanes 3 and 7). Note that HOXA9 is not expressed in acute lymphoblastic leukemias (ALLs); 697 is a pre-B ALL cell line. “No RT” indicates the absence of reverse transcriptase in the reaction. Probe used as indicated, exposure time: 4½ hours for HOXA9 and 2½ hours for actin. (B) Survival curve of recipients of 2 × 105 (day-0 equivalent) BM cells transduced with the indicated retrovirus and grown prior to transplantation for 7 days in vitro with hemopoietic growth factors; “B” refers toBCR-ABL; “H,” to HOXA9; and “N,” toNUP98-HOXA9. (C) Characteristics of leukemias developing in the various bone marrow transplantation chimeras described in panel B. AML, acute myeloid leukemia; % blast evaluated on 100 cells per each mouse. NA indicates data not available.
