Aberrant expression of the major sialoglycoprotein (CD43) on the monocytes of patients with myelodysplastic syndromes.

CD43, a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. The reduced expression of this antigen in patients with Wiscott-Aldrich syndrome, in which progressive immunodeficiency is a major problem, raised the question whether abnormal expression of this molecule could affect the susceptibility to infections in patients with myelodysplastic syndromes (MDS). We studied the expression of this antigen on the monocytes of ten patients with chronic myelomonocytic leukemia (CMML) and compared the results with 67 patients suffering from other MDS syndromes and with 18 healthy individuals. We chose this series as it plays an important role in MDS patients where in most cases the neutrophils are defective. We also examined the following antigens as indicative of activation and adhesion of the monocytes in these patients: CD11b, CD18, CD35, CD38, CD44, CD69. We found decreased expression of CD43 on the monocytes of the RA, RAS, RAEB, and RAEB-t patients compared with the CMML and controls. The other activation molecules studied were found to be upregulated, suggesting the existence of activated monocytes in these patients. The increased levels of soluble vascular cell adhesion molecule in these patients suggest vascular endothelial activation in the absence of infection. Further experiments are needed to investigate the significance of CD43 downregulation in these patients, its role in cell adherence and tissue migration, and the correlation of the phenomenon to the increased susceptibility to infections observed in these patients.

Elevated serum TNF-alpha concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes.

The levels of IL-1 alpha, IL-2, IL-6 and TNF-alpha were measured immunoradiometrically in the sera of 82 myelodysplastic (MDS) patients at diagnosis in an attempt to identify possible relationships between serum cytokine levels and clinical and laboratory parameters of the patients. We found that serum IL-6 and TNF-alpha concentrations were significantly higher in the group of MDS patients than in the normal controls (p < 0.03 and p < 0.001, respectively), while serum IL-1 alpha and IL-2 levels did not differ statistically between patients and control subjects. Elevated serum IL-6 and TNF-alpha concentrations were mainly seen in patients with high-risk myelodysplasia (MDS), i.e. patients with chronic myelomonocytic leukemia (CMML) (p < 0.05 and p < 0.001, respectively), refractor anemia with excess of blasts (RAEB) (p < 0.01 and p < 0.001, respectively), or refrochopy anemia with excess of blasts in transformation to acute leukemia (RAEB-t) (p < 0.001 and p < 0.001, respectively). Patients with low-risk disease, i.e. patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS), had serum cytokine levels comparable to those of controls. Patients' serum IL-6 and TNF-alpha correlated inversely with the hemoglobin concentration (p < 0.01 and p < 0.05, respectively) and positively with the absolute number of circulating myeloblasts (p < 0.01 and p < 0.001, respectively) and the proportion of bone marrow (p < 0.001 and p < 0.001, respectively) myeloblasts. A negative correlation was also noted between serum TNF-alpha concentrations and patients' survival in high-risk MDS (p < 0.02). We concluded that elevated serum IL-6 and TNF-alpha values are seen mainly in patients with high-risk disease, and that high serum TNF-alpha concentrations are predictive of shortened survival in this group of patients.

Serum beta 2 microglobulin in malignant lymphoproliferative disorders.

Serum beta-2-microglobulin (S-beta 2M) was measured at diagnosis in 44 patients with lymphocytic leukemias and 47 with malignant lymphomas. Among patients with chronic lymphocytic leukemia (CLL) S-beta 2M was raised (greater than 3 mg/l) in 74% and in 23.5% of those with acute lymphoblastic leukemia (ALL). The frequencies for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were 59.2% and 40%, respectively. In CLL patients high serum values correlated with large tumor mass, as estimated by Rai's clinical criteria (P less than 0.001), by total peripheral lymphocytes (r = 0.41, P less than 0.05) and by the percentage of bone marrow infiltration of the lymphocytes (P less than 0.01). A significant relation was also found in CLL patients between S-beta 2M level and survival (P less than 0.05). In ALL no association was found between S-beta 2M level with peripheral lymphoblast concentration, French-American-British (FAB) subclassification, splenomegaly, and survival. In NHL patients a significant association was found between S-beta 2M levels and stage of disease (P less than 0.01) and an obscure relation (P less than 0.1) with the presence of lymph nodes greater than 3 cm in diameter, splenomegaly, and hepatomegaly. No significant association was found between S-beta 2M level and histologic subtypes, presence of B symptoms, bone marrow involvement, and survival. In HD patients a significant association was found between the level of S-beta 2M and stage of disease (P less than 0.05) and presence of splenomegaly (P less than 0.05). No association was found between S-beta 2M level and histologic subtypes, lymph nodes greater than 3 cm in diameter, bone marrow involvement, and B symptoms. A significant relation was found between S-beta 2M level and survival in HD patients with widespread disease (P less than .025).