Blood, 1958, Vol. 13, No. 4, pp. 313-338.
© 1958 American Society of Hematology, Inc.
The Nature and Significance of Megaloblastic
Blood Formation
EDWARD H. REISNER JR. 1
1 Department of Medicine, St. Luke’s Hospital, New York, N.Y.
Evidence is presented for a hypothesis that megaloblasts are red blood
cell precursors with a prolonged resting phase between mitoses, allowing a
longer time for dispersion of the chromatin throughout the nucleus. Anything that retards the rate of cell division can produce cells of similar appearance, but the conditions most conducive to megaloblastic blood formation are states in which vitamin B12 or folic acid are deficient. These two
substances function in the synthesis of nucleoproteins as co-enzymes or their
precursors concerned with the transfer of one-carbon units. In their absence
the synthesis of the extra amounts of deoxyribonucleic acid essential for
mitosis can go on but slowly, and the marrow becomes crowded with cells
waiting to divide.
The principle source of the extra DNA is cytoplasmic RNA which appears
to supply the ribonucleotide precursors of several deoxyribose containing
compounds. Most important among these is deoxyuridylic acid which is
methylated to form thymidylic acid. The failure of these reactions to occur
in the absence of the essential co-enzymes leads to a persistence of RNA in
the megaloblastic cytoplasm during the maturation phase, and this is probably
responsible for their development into macrocytes.
This hypothesis accounts for the occasional presence of megaloblasts in
conditions other than pernicious and related deficiency anemias and the occurrence of "macronormoblastic" or "megaloblastoid" marrows in intrauterine
life and liver disease. The hypothesis also explains the rapid replacement of
megaloblasts by normoblasts in the marrow following specific therapy.
Submitted on July 12, 1957
Accepted on August 3, 1957
