Methylated Arginines in Chronic Erythremic Myelosis 1

This report describes the occurrence of methylated arginines in hydrolysates of histones obtained from bone marrow erythroid precursors of five patients with chronic erythremic myelosis (DiGuglielmo's syndrome). Methylated arginines such as those to be described were not found in similar histone hydrolysates obtained from patients with a variety of other disorders of erythropoiesis.

Materials and Methods. Sternal or iliac bone marrow was obtained in a heparinized glass syringe immediately after the diagnostic aspiration from five patients with chronic erythremic myelosis. All of these patients had refractory macrocytic anemia with splenomegaly and intense megaloblastoid erythroid hyperplasia of the bone marrow. Four of the patients had at least 20% proerythroblasts in the marrow, and one patient had as high as 40% proerythroblasts. A PAS (periodic acid-Schiff) stain on the marrows revealed PAS-positive material within the cytoplasm of proerythroblasts, and a Prussian blue stain disclosed many ringed sideroblasts and abundant stainable iron. Samples of bone marrow were also obtained from three patients with untreated classical pernicious anemia, from three patients with pernicious anemia 20 hr after their initial dose of vitamin B12, and from two patients with autoimmune hemolytic anemia. Since all of the bone marrows were composed largely (up to 90%) of erythroid precursors and because the sample amounts were restricted to that obtainable during a routine aspiration, no efforts to fractionate marrow samples were made. From 60-70 mg of marrow flecks, lysine-rich and arginine-rich histones were extracted by methods described previously (1), and approximately 400 μg of each type of histone was obtained.

The histones were hydrolyzed for 24 hr in 6 N HC1 and evaporated to dryness in a rotary evaporator. Each sample of histone yielded approximately 300 μg total amino