ANOMALOUS PLASMA-CONCENTRATIONS AND IMPAIRED SECRETION OF GROWTH-FACTORS IN FANCONIS ANEMIA

In Fanconi's anemia, which is known to be an autosomal recessive Mende lian trait with four complementary groups. In addition to stunning phe notypic variation at clinical and cellular levels, aplastic pancytopen ia is a common feature. Since either an early block of differentiation in stem cells or their insufficient support by stromal functions coul d be an underlying factor, levels of stem cell factor (SCF) and cytoki nes have been measured in blood and in supernatants of monocytes after stimulation with granulocyte-macrophage colony stimulating factor (GM -CSF). In two of three FA patients, no GM-CSF was detectable, and simu ltaneously SCF was decreased to 8% and 15% of normal values. The combi nation of low SCF and GM-CSF may be implied in the pathogenesis of mar row aplasia, since comparison with W/Sl mice shows that impairment of the SCF/c-kit function alone has different effects. Also, this explain s that treatment with GM-CSF in a recent study enhanced only leukogene sis and not all three lineages. In the third patient, both factors wer e normal, and here a different mechanism may act. In all three FA pati ents, interleukin 6 (IL-6) production in stimulated monocytes was decr eased, which may hamper immune defense of infections in a nonspecific way.