Serum stem cell factor concentration in patients with myelodysplastic syndromes.

Stem cell factor (SCF) is characterized by its capacity to synergize dramatically with other haemopoietic growth factors in in vitro erythroid, myeloid, and lymphoid progenitor culture systems. We have measured serum SCF concentrations by enzyme immunoassay in 85 patients with myelodysplasia (MDS). Serum samples were taken in 1988-89 and in 1991-92 and stored at -20 degrees C. Mean serum SCF concentration in the MDS patients was 2.81 ng/ml (range 0.6-8.0). This was significantly lower (P = 0.0001) than the values for 234 normal subjects; mean 3.30 ng/ml (range 1.3-8.0). No significant relationship between SCF concentration and peripheral blood counts, bone marrow parameters, red cell transfusion status, survival or FAB subtype was found, although a trend of decreasing SCF concentration from refractory anaemia through sideroblastic anaemia and chronic myelomonocytic leukaemia to refractory anaemia with excess blasts was seen. The reduced SCF serum concentration in some patients with myelodysplasia suggests a rationale for therapy with recombinant SCF in these patients.

Levels of soluble stem cell factor in serum of patients with aplastic anemia.

Aplastic anemia (AA) is a rare bone marrow (BM) disorder characterized by an unexplained failure of hematopoietic precursors to proliferate. In vitro growth of AA BM cells can be improved by the addition of the hematopoietic growth factor SCF (stem cell factor), which suggests that deficiency of SCF may be one of the underlying causes of the disease. In this study, we measured the concentration of SCF in sera of patients with severe AA. One hundred twenty-eight serum samples from 32 patients, at diagnosis and following therapy, were analyzed. Before treatment, SCF levels varied between 0.33 and 6.1 ng/mL; no correlation between hematopoietic function and SCF serum levels was apparent. Therapy with antilymphocyte globulin (ALG) or bone marrow transplantation (BMT) did not result in a recognizable pattern of changes in SCF levels. However, serum concentration of SCF in many patients with AA was at the low range of control serum levels determined in healthy blood donors. Of 128 AA serum samples tested before and after therapy, 107 were below the mean normal value of 3.3 ng/mL, including 26 samples below the minimum normal value of 1.3 ng/mL, as estimated in 267 controls. We also found that SCF levels in peripheral blood serum correlate well with factor concentrations in the BM plasma. Clinical observations suggest that higher SCF serum levels are often associated with a better clinical status of the patients in terms of survival and transfusion requirements. The data indicate that a deficient production of soluble SCF may contribute to AA in some patients; thus, suggesting a potential therapeutic benefit of SCF in this disorder.

Decreased endogenous circulating Steel factor (SLF) levels following allogeneic and autologous BMT: lack of an inverse correlation with post-BMT myeloid engraftment.

We have previously demonstrated an inverse relationship between circulating endogenous G-CSF levels and myeloid engraftment post-BMT. A new early-acting hematopoietic growth factor, Steel factor (SLF), has recently been demonstrated to induce the proliferation of early hematopoietic progenitor cells and synergistically stimulate committed progenitor cells in the presence of lineage-specific CSFs. In this pilot study, we determined the temporal relationship between endogenous SLF levels and the circulating absolute neutrophil count (ANC) (myeloid engraftment) in both children and adults undergoing both allogeneic and autologous BMT. Pre-BMT SLF levels were 2600 +/- 100 pg/ml compared to significantly lower levels of G-CSF (30-50 pg/ml). The circulating SLF level was significantly decreased throughout the post-BMT period (ANC < or = 200 x 10(6)/l: 1500 +/- 600 pg/ml; ANC 200-500 x 10(6)/l: 1780 +/- 130 pg/ml; ANC > or = 500 x 10(6)/l: 1690 +/- 110 pg/ml) (p < 0.001). There was a lack of an inverse relationship between the circulating SLF level and the ANC (r = -0.43) (p = NS). For comparison, SLF levels from immune thrombocytopenia (platelet < = or 20 x 10(9)/l) and chemotherapy-induced neutropenia patients (ANC < or = 200 x 10(6)/l) were similar to pre-BMT levels but significantly higher than post-BMT levels (p < or = 0.02 and < or = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble stem cell factor in human serum.

Stem cell factor (SCF) is a recently described factor active in the early stages of hematopoiesis. It can exist in membrane-bound form and in proteolytically released soluble form. The levels and nature of SCF in human serum are described. As determined by an enzyme-linked immunosorbent assay performed for 257 samples, SCF level in serum averaged 3.3 +/- 1.1 ng/mL. The serum SCF was partially purified by immunoaffinity chromatography and analyzed by glycosidase treatments in conjunction with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The results show that the SCF has N-linked and O-linked carbohydrate and corresponds to the soluble form, at or about 165 amino acids in length. The findings suggest functional importance for soluble SCF in humans.

Evaluation of creatine kinase and lactate dehydrogenase activities in clinically normal and abnormal equine joints.

Creatine kinase (CK) and lactate dehydrogenase (LD) enzyme activities and isoenzymes were determined for synovial fluid, synovial membrane, and articular cartilage from 24 clinically normal equine tarsocrural (tibiotarsal) and femoropatellar joints. All 3 tissues contained LD isoenzymes LD1 to LD5, and CK isoenzymes BB and MM. The CK isoenzyme MB was not found. The similarities in isoenzyme composition of these 3 tissues made differentiation of the source of LD and CK impossible by isoenzyme pattern alone. Reference values for the total enzyme activities of specific joint tissues also had wide variations. The wide variation in activities, as determined by the enzymatic analysis of synovial fluid and a lack of tissue specificity in clinically normal equine joint tissue, indicated that those values were not predictive for the extent and type of tissue damage in equine joint disease. This hypothesis was confirmed when synovial fluids from 22 abnormal joints were analyzed for LD isoenzymes and total enzyme activity. The various causes of the joint problems were not distinguishable.