In the fully-developed megaloblast of vitamin B12 or folate deficiency, unique alterations occur in the chromatin adherent to the nuclear membrane. This chromatin is often tenuously connected to or separated from other chromatin, and gives the nucleus a clockface appearance. A clockface chromatin pattern appears only rarely in "megaloblastoid" erythroblasts from cases of refractory megaloblastic anemia. Normal erythroblasts and developing erythroblasts from a variety of anemias do not exhibit this chromatin pattern. Although the pathogenesis of the "clockface sign" is unknown, alterations in megaloblast histone might cause both the clockface chromatin pattern and subsequent chromosomal abnormalities. When the "clockface sign" appears in an intermediate megaloblast, it may provide a morphological clue to a deficiency of vitamin B12 or folate.

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