ALBERT

Description: 1. Normal gastric juice (intrinsic factor) and vitamin B12 together form a thermolabile hemopoietic factor which ripens megaloblasts in vitro, both gastric juice and B12 alone being inactive. 2. The hemopoietic factor in normal serum which ripens megaloblasts in vitro also appears to be thermolabile, heating to 56 C. for 2 hours destroying some of its activity. 3. The relationship of these factors is discussed and an extra-gastric as well as a gastric source of intrinsic factor is postulated.

Description: Differential Diagnosis. An unresponsive anemia associated with a leukoerythroblastic peripheral blood picture may be seen in such varying clinical conditions as carcinomatosis, leukemia in early phase, Hodgkin’s disease, toxic aplastic anemia, hemolytic anemia, myelosclerosis, myeloma, syphilis, tuberculosis, lipoidosis, Leishmaniasis and infective hepatitis. From the clinical course of the disease and routine methods of investigation, the majority of these diseases could be excluded. It was soon apparent from the appearance of the marrow and the result of the marrow culture that this disease was to be regarded as a primary blood dyscrasia. There is a group of such dyscrasias which is characterized by abnormalities in both erythro- and leukopoiesis. All gradations between erythremic myelosis (Copelli,2 Guglielmo,3 Leitner et al.6) and myeloblastic leukemia may occur. The case here described is neither one of erythremic myelosis nor one of acute leukemia. Heilmeyer and Schöner5 describe a true chronic erythroblastosis of adults which, however, is accompanied by a leukocytosis, never present in this case. Several transitional cases, where there is neither a predominant erythroblastic nor a proponderating myeloblastic hyperplasia, have been reported. In these there is, however, evidence of a neoplastic hyperplasia of both erythroid and myeloid tissue. Such cases have been described by Penati,10 Moeschlin,7 Moeschlin and Rohr,8 Rohr,11 Harvier et al.,4 and Stahel.12 The course of six months in the present case resembles that of Moeschlin.7 It is of academic interest to differentiate between a true aplastic anemia, an aplastic initial phase of leukemia and the mixed neoplastic forms of the erythroleukemic group. Etythroblasts in cases of this group frequenfly show "megaloid" changes (as do those in acute leukemia). A series of transitional forms from normoblasts to megaloblasts through "megaloid" forms may be seen. This could be due to a relative deficiency in nutritive factors consequent on the abnormal cellular proliferation. Similarly in many types of acute leukemia this type of cell, when cultured in normal serum, reverts to the normal maturation rate and morphology of the normoblast. So do the cells of aplastic anemia, where the ultimate defect is further removed. When, however, an abnormal normoblastic maturation rate is found, a qualitative, probably neoplastic, change in the nature of these cells is suggested, since the same changes may be found in the myeloid series in cases of myeloid leukemia. Hence marrow culture may prove of diagnostic value in differentiating these somewhat allied conditions. This case is one of progressive, irresponsive anemia with a peripheral leukoerythroblastosis, and bone marrow showing a considerably lowered leukoerythrogenetic ratio with a relative myeloid predominance of early forms and of atypical blast cells (paramyeloblasts). Culture of the bone marrow established that the rate of maturation of both the erythroid and myeloid tissue was abnormal, although the defect was more marked in the erythroid series. On these findings a diagnosis of erythroleukemia seems justified. Since this report, 2 similar cases investigated by marrow culture have shown comparable maturation abnormalities.

Description: As assessed by its spleen colony-forming ability, the stem cell content of bone marrow from mice recovering from hypoxia increases with the duration of erythropoietic depression, and is directly proportional to the number of marrow lymphocytes.