Bone Marrow Erythroblastic Dysplasia on Morphology Correlates Significantly with Flow Cytometric Apoptosis and Peripheral Blood Eryptosis.

Abstract

Introduction: Erythrocytic damage and death in response to physiochemical, infectious, metabolic, and pharmacological insults have been extensively studied in several diseases. Their relationship with erythroid precursors' apoptosis and morphological dysplasia, however, remains largely unexplored, despite several shared triggers and pathogenetic mechanisms.

Materials and methods: We compared peripheral blood phosphatidylserine (PS) exposure and calcium influx in 53 patients with early and late apoptosis of CD71 + ve marrow erythroblasts using flow cytometry. Flow cytometric results were then correlated with dyserythropoiesis in the bone marrow as scored by experienced morphologists.

Results: Median patient age was 32 years (range: 1-75 years); 38 (72%) had hemoglobin (Hb) ≤11.0 g%. Patients overall had significantly higher Annexin V binding (PS exposure) and Fluo-3AM signal (calcium influx) vis-à-vis 20 healthy controls. Dyserythropoiesis on morphological evaluation correlated significantly with PS exposure (r = 0.618, P = 0.014) and Fluo-3AM binding (P = 0.002). Patients with dyserythropoiesis had significantly higher apoptosis compared to those without dyserythropoiesis (P = 0.006). In the peripheral blood, Annexin V binding and Fluo-3AM fluorescence correlated strongly with each other (r = 0.885, P < 0.001). PS exposure and Ca²⁺ influx were increased in 64% of cases. These patients had significantly lower Hbs and reticulocyte counts and increased red cell distribution widths and circulating nucleated red blood cell numbers.

Conclusions: This is the first study to compare and demonstrate links between dyserythropoiesis, peripheral blood eryptosis, and erythroblastic apoptosis. Eryptosis and apoptosis' interrelationships in patients with diverse hematological disorders link the marrow environment to peripheral blood.