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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4395-4405
Lineage-Specific Modulation of Calcium Pump Expression During
Myeloid Differentiation
Sophie Launay,
Maurizio Giannì,
Tünde Kovàcs,
Raymonde Bredoux,
Arlette Bruel,
Pascal Gélébart,
Fabien Zassadowski,
Christine Chomienne,
Jocelyne Enouf, and
Béla Papp
From U. 348 INSERM, IFR Circulation Lariboisière, Hôpital
Lariboisière, Paris, France; CNRS UPR 9051, INSERM U. 301, and
CNRS EP 107, Hôpital Saint Louis, Paris, France; and the National
Institute of Haematology, Budapest, Hungary.
Calcium is accumulated from the cytosol into the endoplasmic
reticulum by sarco-endoplasmic reticulum calcium transport ATPase (SERCA) enzymes. Because calcium stored in the endoplasmic reticulum is
essential for cell growth, differentiation, calcium signaling, and
apoptosis and because different SERCA enzymes possess distinct functional characteristics, in the present report we explored SERCA
expression during in vitro differentiation of the human myeloid/promyelocytic cell lines HL-60 and NB4 and of freshly isolated
acute promyelocytic leukemia cells. Two SERCA species have been found
to be coexpressed in these cells: SERCA 2b and another isoform,
SERCAPLIM, which is recognized by the PLIM430 monoclonal
antibody. Induction of differentiation along the neutrophil granulocytic lineage by all-trans retinoic acid or cyclic AMP analogs led to an increased expression of SERCAPLIM,
whereas the expression of the SERCA 2b isoform was decreased. The
modulation of SERCA expression was manifest also on the mRNA level.
Experiments with retinoic acid receptor isoform-specific retinoids
indicated that SERCA expression is modulated by retinoic acid receptor
 -dependent signaling. SERCA expression of retinoic acid-resistant
cell variants was refractory to treatment. Differentiation along the
monocyte/macrophage lineage by phorbol ester resulted in an increased
expression of both SERCA isoforms. In addition, when cells were treated
by phorbol ester in the presence of the glucocorticoid dexamethasone, a
known inhibitor of monocyte differentiation, a selective blockage of the induction of SERCAPLIM was observed. Altered SERCA
expression modified the functional characteristics of calcium transport
into the endoplasmic reticulum. These observations show for the first time that the modulation of calcium pump expression is an integral component of the differentiation program of myeloid precursors and
indicate that a lineage-specific remodelling of the endoplasmic reticulum occurs during cell maturation. In addition, these data show
that SERCA isoforms may serve as useful markers for the study of
myeloid differentiation.
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