Chromosomal translocations are commonly found in de novo acute myeloid leukemia (AML) cells, and the fusion proteins produced from these genetic abnormalities are assumed to contribute directly to leukemogenesis and/or progression. The AML1/ETO fusion protein, created by translocations between chromosomes 8 and 21 [t(8;21); G. Nucifora and J. D. Rowley, Leuk. Lymphoma, 14: 353-362, 1994; K. L. Rhoades et al., Proc. Natl. Acad. Sci. USA, 93: 11895-11900, 1996] can induce anti-apoptotic Bcl-2 expression in vitro and was proposed to thereby promote the survival of t(8;21)-bearing AML cells (L. Klampfer et al., Proc. Natl. Acad. Sci. USA, 93: 14059-14064, 1996). We confirm that cells of the t(8;21)-bearing Kasumi cell line do express high levels of Bcl-2 protein, as reported previously. However, we show that primary AML cells with (8;21) chromosomal translocations generally express low levels of Bcl-2 protein relative to normal bone marrow-derived myeloid cells and to AML samples with other simple karyotypic abnormalities. We note that p53 mutations are present in the myeloid cell lines expressing AML-ETO protein from chromosomal translocations (Kasumi and SKNO) or from transfected fusion genes (U937) but were undetected in our analyses of 28 primary t(8;21)-bearing AML cell samples from de novo AMLs. Because wild-type p53 can transcriptionally down-regulate bcl-2, we speculate that p53 mutations may contribute to the association of t(8;21) chromosomal abnormalities with higher Bcl-2 expression levels in leukemia cell lines. We also note that some t(8;21)-bearing samples from pediatric and older adult patients do express somewhat higher levels of Bcl-2 than t(8;21)-bearing samples from young adult patients. This suggests that Bcl-2 overexpression could occur in these AML cells by an as yet undefined, p53-independent mechanism and could contribute to the reported association of t(8;21) karyotypes with poor clinical outcomes in childhood AML patients and/or to typically poor clinical outcomes in elderly AML patients.

This content is only available via PDF.