Stromal-mediated down-regulation of CD13 in bone marrow cells originating from acute myeloid leukemia patients

The metallopeptidase CD13 is expressed on normal myeloid cells of monocytic and granulocytic origin and on the surface of leukemic blasts in most acut e myeloid leukemias (AML). To study the mechanisms regulating lineage restr icted CD13 expression in AML we determined normalised CD13 mRNA levels in b one marrow cells and peripheral blood cells of 27 AML patients. Cells of bo ne marrow origin had lower levels of normalised CD13 mRNA than cells of per ipheral blood origin, even though fluorescence intensity and fraction of ce lls expressing CD13 on the surface was unchanged. In particular, AML patien ts with very low levels of normalised CD13 mRNA in bone marrow cells showed an increase in CD13 mRNA expression in peripheral blood. To evaluate the e ffects of bone marrow microenvironment on CD13 mRNA expression, we cultured leukemic myeloid cells with and without murine stromal cells. Bone marrow cells with high and low CD13 surface expression that entered the stromal la yers all downregulated CD13 mRNA expression as compared to cells in suspens ion above. For peripheral blood cells within stromal layers, CD13 mRNA expr ession was diminished in only 3 out of 6 cases. The ambiguous effect of str omal cells on peripheral blood cells may illustrate a differentiation-depen dent response towards stroma. We determined the polyadenylation status of C D13 mRNA for 9 bone marrow aspirates and 7 peripheral blood samples. Polyad enylation was diminished in bone marrow cells from AML patients with low le vels of normalised CD13 mRNA, raising the possibility of involvement of mRN A instability in regulation of CD13 mRNA expression in this subgroup of pat ients.