This review summarises current understanding of the haemopoietic defect in
Diamond Blackfan anaemia (DBA). In vitro clonogenic cultures of bone marrow
cells from DBA patients have demonstrated variable patterns. Erythroid pro
genitors may be absent, reduced or sometimes normal or near - normal. This
may be due to defective differentiation of haemopoietic cells along the ery
throid lineage, either in terminal differentiation after the CFU-E stage or
at an earlier stage of erythropoiesis, and possibly involving the multipot
ent CFU-Mix since CFU-GM may also be reduced in some patients. Erythroid pr
ogenitors are relatively insensitive to erythropoietin (EPO) in vitro, and
haemopoietic growth factors such as interleukin-3 (IL-3) or stem cell facto
r (SCF) can partially correct this insensitivity in vitro. Insensitivity to
EPO may explain the accelerated degree of apoptosis of DBA erythroid proge
nitors compared with normal, and the lack of haematological response when t
he drug is administered to patients with DBA. Although the addition of IL-3
or SCF to DBA bone marrow cells in vitro results in significant increase i
n number, size and degree of haemoglobinisation of erythroid progenitors, o
nly a small percentage of patients respond to IL-3 in vivo. Possible explan
ations for the lack of correlation between in vitro and in vivo effects of
IL-3 are discussed. It has only recently become apparent that patients with
DBA have an increased risk of acute myeloid leukaemia, and also can later
develop aplastic anaemia. In vitro clonogenic cultures have revealed reduce
d numbers of GFU-GM and CPU-Mix in some patients. The involvement of other
haemopoietic cell lineages other than the erythroid lineage in DBA may occu
r more frequently than previously appreciated, although to date there have
been very few in vitro studies assessing this in detail in DBA.