Blood, 15 March 2002, Vol. 99, No. 6, pp. 1883-1883
Life and death of multiple myeloma cells
Multiple myeloma (MM) is a B-cell malignancy in which plasma
cells have decreased proliferative ability and an extended lifespan. Zhang and colleagues (page 1885) set out to identify the molecular processes responsible for this extended survival (or delayed apoptosis) in MM cells.
First they showed (using inhibitors of transcription and protein
turnover) that survival of MM cells appeared to require the continuous
expression of a protein with a high turnover rate. MM cells express a
number of survival proteins (of the Bcl-2 family), but changes in
levels of one of these, myeloid cell factor-1 (Mcl-1), paralleled changes in cell survival. Thus when Mcl-1 levels were low, the MM cells underwent apoptosis, while levels of Mcl-1 were high
in nonapoptotic cells. This correlation by itself was not sufficient to
determine whether changes in Mcl-1 levels were actually driving, or
merely reflecting, cell death or survival. They then used antisense
oligonucleotides or transfection with Mcl-1 cDNA to specifically
decrease or increase, respectively, cellular levels of Mcl-1.
These approaches confirmed the earlier conclusions: knocking out Mcl-1
levels induced apoptosis and increasing Mcl-1 levels gave the cells
even greater resistance to cell death.
Zhang and colleagues show that increased expression of a single
survival protein, Mcl-1, may be sufficient to confer the malignant phenotype in MM cells. Apart from providing important new insights into
the molecular pathology of MM cells, this work could lead to the
development of new therapeutic strategies for the treatment of MM based
on the targeted disruption of Mcl-1 expression.
Steven W. Edwards
University of
Liverpool
