Proerythroblasts

Proerythroblast is the earliest identifiable cell in the erythroid lineage during erythropoiesis. It arises from the erythroid progenitor CFU-E under the influence of erythropoietin (EPO) and marks the transition from committed progenitors to mature red cell precursors. In adults, erythropoiesis occurs in the bone marrow, where proerythroblasts reside in erythroblastic islands that include a central macrophage to support development and assist in the clearance of nuclei during later stages.

Morphology and characteristics: Proerythroblasts are relatively large cells with a large nucleus occupying much of the cell. The nucleus shows fine chromatin and often one or more prominent nucleoli. The cytoplasm is deeply basophilic due to abundant RNA and ribosomes, reflecting limited hemoglobin synthesis at this stage. Cells are capable of several mitotic divisions before hemoglobin production increases.

Developmental progression: Proerythroblasts differentiate into basophilic erythroblasts, then polychromatic erythroblasts and eventually orthochromatic erythroblasts, which expel their nuclei to form reticulocytes and mature erythrocytes. EPO receptor signaling and transcriptional programs, including GATA-1, drive this differentiation. Iron uptake and globin synthesis become prominent in the later stages of erythroid maturation.

Clinical relevance: Abnormalities in proerythroblast development or proliferation are associated with disorders such as Diamond-Blackfan anemia, which involves erythroid progenitor defects, and pure red cell aplasia, which features selective erythroid lineage failure. In some leukemias, particularly acute erythroid leukemia, malignant proliferation of erythroid precursors includes the proerythroblast population within the bone marrow.