Loss of Full-Length GATA1 Expression in Megakaryocytes Is a Sensitive and Specific Immunohistochemical Marker for the Diagnosis of Myeloid Proliferative Disorder Related to Down Syndrome

Objectives: Myeloid proliferative disorders associated with Down syndrome (MPD-DS), including transient abnormal myelopoiesis and myeloid leukemia associated with Down syndrome (DS), harbor mutations of GATA1, a transcription factor essential for erythroid and megakaryocytic development. These mutations result in a N-terminally truncated GATA1 (GATA1s) and prohibit the production of the full-length GATA1 (GATA1f). Here, we demonstrate the utility of immunohistochemical GATA1f reactivity in diagnosing MPD-DS. Methods: Immunohistochemical studies for GATA1f expression were performed on bone marrow biopsy specimens. Results: In all cases of MPD-DS, megakaryocytes lacked GATA1f expression. In contrast, GATA1f expression was detected in megakaryocytes in all specimen types from patients without DS (normal bone marrows, pediatric myelodysplastic syndrome, juvenile myelomonocytic leukemia, adult acute megakaryocytic leukemia [pediatric and adult; without trisomy 2]), as well as normal bone marrows from patients with DS. Conclusions: The lack of GATA1f expression is a sensitive and specific immunohistochemical marker for MPD-DS.