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PubMed · 704501

Megaloblastic anemia.

Abstract

Most, but not all, megaloblastic anemia is produced by "ineffective erythropoiesis" in the bone marrow due to either folic acid or vitamin B12 deficiency. In folic acid deficiency the cause frequently is inadequate dietary intake, whereas vitamin B12 deficiency is almost always conditioned by some specific type of malabsorption. Anemia with oval macrocytes, few reticulocytes, moderate leukopenia, and thrombocytopenia is typical of both. Aplastic anemia, refractory anemias with cellular marrow, preleukemia, aleukemia, and erythroleukemia may have somewhat similar blood findings but are usually recognizable from bone marrow biopsy. Decreased levels of folate or vitamin B12 are the most reliable criteria of megaloblastic anemia. With these available in advance, therapy with the appropriate vitamin can be begun at once. If serum levels are unavailable or available only in retrospect, initial treatment, especially of severe anemia, should be with both vitamins. Differentiation between folate and vitamin B12 deficiency is important but impossible by blood and bone marrow morphology alone. Thus, if serum levels are unavailable, the distinction must be made, sometimes retrospectively, on the basis of other laboratory examinations, such as gastric analysis, small-bowel x-ray films, and the Schilling test.

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BibTeXRIS

W B Castle. 1978. Megaloblastic anemia.. https://doi.org/10.1080/00325481.1978.11714952

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E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation.

The E2F proteins are major regulators of the transcriptional program required to coordinate cell cycle progression and exit. In particular, E2f4 has been proposed to be the principal family member responsible for the regulation of cell cycle exit chiefly through its transcriptional repressive properties. We have previously shown that E2f4(-/-) mice display a marked macrocytic anemia implicating E2f4 in the regulation of erythropoiesis. However, these studies could not distinguish whether E2f4 was required for differentiation, survival, or proliferation control. Here, we describe a novel function for E2f4 in the promotion of erythroid proliferation. We show that loss of E2f4 results in an impaired expansion of the fetal erythroid compartment in vivo that is associated with impaired cell cycle progression and decreased erythroid proliferation. Consistent with these observations, cDNA microarray analysis reveals cell cycle control genes as one of the major class of genes down-regulated in E2f4(-/-) FLs, and we provide evidence that E2f4 may directly regulate the transcriptional expression of a number of these genes. We conclude that the macrocytic anemia of E2f4(-/-) mice results primarily from impaired cellular proliferation and that the major role of E2f4 in fetal erythropoiesis is to promote cell cycle progression and cellular proliferation.

Anemia, Macrocytic↗