PERTURBATION IN THE ABILITY OF BONE-MARROW STROMA FROM PATIENTS WITH ACUTE MYELOID-LEUKEMIA BUT NOT CHRONIC MYELOID-LEUKEMIA TO SUPPORT NORMAL EARLY HEMATOPOIETIC PROGENITOR
Rl. Sparrow et al., PERTURBATION IN THE ABILITY OF BONE-MARROW STROMA FROM PATIENTS WITH ACUTE MYELOID-LEUKEMIA BUT NOT CHRONIC MYELOID-LEUKEMIA TO SUPPORT NORMAL EARLY HEMATOPOIETIC PROGENITOR, Leukemia research, 21(1), 1997, pp. 29-36
The ability of bone marrow (BM) stroma derived from patients with acut
e myeloid leukemia (AML) or chronic myeloid leukemia (CML) to support
normal hematopoiesis was investigated using a two-stage long-term bone
marrow culture (LTBMC) procedure. Of particular interest was whether
leukemia-derived stroma were capable of supporting the very immature,
uncommitted hematopoietic progenitor cells (HPC) which are considered
to have a higher dependence and association with the BM stroma than th
e more mature committed HPC. Confluent stromal layers were recharged w
ith selected populations of normal HPC enriched for the CD34(+)CD38(-)
cells (immature, uncommitted HPC) or the CD34(+)CD38(+) cells (mature
, committed HPC). The weekly output of clonable granulocyte-macrophage
progenitor cells (CFU-GM) was used as an indicator of the hematopoiet
ic-supporting ability of the cultures. Stromal layers derived from 5/7
patients newly diagnosed with AML, showed significantly depressed abi
lity to support the CD34(+)CD38(-) cells compared to stroma derived fr
om normal donors. The supporting function of the AML-derived stroma fo
r the more mature CD34(+)CD38(+) cells was similar to that of the norm
al stroma (3/3 cases). Stromal layers derived from patients with chron
ic-phase CML showed normal or enhanced supporting function for the CD3
4(+)CD38(-) cells (5/6 cases), and likewise for the CD34(+)CD38(-) cel
ls (3/3 cases). This study revealed a selective defect in the ability
of BM stroma from patients with AML to support the maturation of norma
l early uncommitted HPC, represented by the CD34(+)CD38(-) cells, whil
st the ability to support the committed CD34(+)CD38(+) cells was not a
ffected. This suggests that the BM microenvironment may be implicated
in the disease mechanism of AML. It does not, however, appear to be as
clearly implicated in chronic-phase CML. (C) 1997 Elsevier Science Lt
d.