of cell death is critical for tumorigenesis and it is widely believed
that expression of pro-survival Bcl-2 family members is
essential to sustain survival of cells undergoing neoplastic transformation.
Previous studies have shown that Bcl-xL, is critical for Myc-induced pre-B/B lymphoma
development. It remains, however, unclear whether Bcl-xL is the sole
pro-survival Bcl-2 family member required for Myc-induced tumorigenesis. Mcl-1 is
critical for cell survival during the early stages of B lymphopoiesis and is
expressed at abnormally high levels in several types of human B cell lymphomas
where it causes chemo-resistance. We therefore examined the
role of Mcl-1 in lymphoma development in Eµ-myc transgenic mice, a model of human Burkitt’s
lymphoma, in which Myc over-expression under control of the immunoglobulin
heavy chain gene enhancer (Eµ) causes accumulation of
pre-leukaemic pro-B/pre-B cells, which further progress to a malignant state. Remarkably, our results show
that loss of only one allele of mcl-1
is sufficient to diminish the pre-leukaemic expansion of B lymphoid cells and
to substantially prolong survival of Eµ-myc transgenic mice.