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 cells.
The ability of bone marrow (BM) stroma derived from patients with acute 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 the more mature committed HPC. Confluent stromal layers were recharged with 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 hematopoietic-supporting ability of the cultures. Stromal layers derived from 5/7 patients newly diagnosed with AML, showed significantly depressed ability to support the CD34+CD38- cells compared to stroma derived from normal donors. The supporting function of the AML-derived stroma for the more mature CD34+CD38+ cells was similar to that of the normal stroma (3/3 cases). Stromal layers derived from patients with chronic-phase CML showed normal or enhanced supporting function for the CD34+CD38- cells (5/6 cases), and likewise for the CD34+CD38+ cells (3/3 cases). This study revealed a selective defect in the ability of BM stroma from patients with AML to support the maturation of normal early uncommitted HPC, represented by the CD34+CD38- cells, whilst the ability to support the committed CD34+CD38+ cells was not affected. 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.
Sparrow
R L
RL
Clinical Haematology and Bone Marrow Transplantation Research Unit, Alfred Hospital, Prahran, Victoria, Australia.
O'Flaherty
E
E
Blanksby
T M
TM
Szer
J
J
Van Der Weyden
M B
MB
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D003114:Colony-Forming Units Assay; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017154:Stromal Cells / Q000502:physiology