Myelodysplastic syndrome (MDS) における好中球スーパーオキサイド産生能に関する研究

Myelodysplastic syndrome (MDS) are hematological disorders with the potential of progressing to acute leukemia. MDS patients occasionally die of infection despite the absence of severe pancytopenia prior to overt leukemia. Superoxide anion (O(2)(－)) production leads to intracellular bactericidal activity by neutrophils, particularly in an oxygen-dependent system. In this paper, O(2)(－) production by neutrophils in 15 MDS patients [11 patients with refractory anemia with excess of blasts (RAEB) and 4 patients with RAEB in transformation (RAEB-t)] was examined to evaluate possible causes of enhanced susceptibility to infection and to gain information concerning the pathophysiology and prognosis. The following results were obtained : (1) The O(2)(－) production by neutrophils (O(2)(－) production) in 15 MDS patients was lower than that in healthy controls (3.75±2.93 vs 6.20±1.53 nmol/min/10(6) neutrophils, p<0.05). Three of the 15 MDS patients showed little O(2)(－) production. (2) There was inverse correlation between O(2)(－) production and the percentage of leukemic cells in the marrow in acute leukemia (r=0.55, p<0.01), but not in MDS. (3) The O(2)(－) production in 5 MDS patients showing morphological anomalies in a high percentage of neutrophils significantly lower than that in 10 MDS patients showing morphological anomalies in a low percentage of neutrophils (1.04±1.37 vs 5.15±2.50 nmol/min/10(6) neutrophils, p<0.05). (4) The O(2)(－) production in 5 patients with frequent fever (≧38℃) -episodes was significantly lower than that in 10 MDS patients with infrequent fever-episodes (2.22±2.15 vs 4.49±2.83 nmol/min 10(6) neutrophils, p<0.05). (5) Comparison of the O(2)(－) production between MDS patients with and without progression to overt leukemia showed no significant difference (4.25±3.26 vs 3.28±2.76 nmol/min/10(6) neutrophils). These findings suggest that impaired O(2)(－) production by neutrophils, probably due to the faulty differentiation from abnormal hematopoietic clones, is one possible cause of enhanced susceptibility to infection in MDS, and may provide clues for clinical management of infection, but is not useful for early detection of progression to overt leukemia.

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