Summary. Transforming growth factor b (TGF-b) 1 is a ubiquitous bifunctional cytokine implicated in the regulation of haemopoietic stem cells and bone marrow stromal cells. We analysed sera from 63 patients with aplastic anaemia and describe a signi®cant reduction of TGF-b1 that was directly related to their treatment status. Untreated patients (n 35), patients who did not respond (n 15) and those with a partial response (n 23) to treatment had signi®-cantly lower TGF-b1 than the normal control group (n 55), P < 0´0001, P < 0´0001 and P 0´002 respectively. Patients in complete remission (n 15) exhibited TGF-b1 serum levels comparable to the control group. In addition, there was a correlation (r 0´83, P < 0´0001) between serum TGF-b1 and platelet count at time of sample. We have demonstrated that the primary source of TGF-b1 in peripheral blood mononuclear cell (PBMC) cultures was not CD3-positive cells. These data indicate aplastic anaemia is associated with a decreased TGF-b1 expression in peripheral blood circulation, which may be a direct consequence of thrombocytopenia.In vitro stromal layers grown from aplastic patient bone marrow (n 14) produced signi®cantly lower levels of TGF-b1 (P 0´02) when compared to normal stroma (n 15). In the aplastic anaemia bone marrow compartment we postulate that accessory cells down-regulate TGF-b1 expression to allow stem cell cycling to counteract hypoplasia. As TGF-b1 is important in the regulation of haemopoiesis, dysregulation of this cytokine in combination with previously described abnormal cytokine expression may contribute signi®cantly to the pathophysiology of aplastic anaemia by exacerbating primary stem cell defects.

It has previously been shown that patients with aplastic anemia (AA) have a stem cell defect both of proliferation and differentiation. This has been shown by long-term bone marrow (BM) culture, long-term initiating cell assays, and committed progenitor assays. We present, for the first time, data on megakaryocyte ( We have now shown that Mk colony formation from purified BM CD34 + cells is significantly reduced, supporting previous evidence that AA results from a stem cell defect.