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

American Journal of Clinical Pathology
Winston Y LeeGeraldine S Pinkus

Abstract

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. Immunohistochemical studies for GATA1f expression were performed on bone marrow biopsy specimens. 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. The lack of GATA1f expression is a sensitive and specific immunohistochemical marker for MPD-DS.

References

Aug 13, 2002·Nature Genetics·Joshua WechslerJohn D Crispino
Jul 1, 2011·Blood·Kate A AlfordUNKNOWN International Myeloid Leukemia-Down Syndrome Study Group
Jun 19, 2012·The Journal of Clinical Investigation·Vijay G SankaranHanna T Gazda
Aug 27, 2014·British Journal of Haematology·Irene Roberts, Shai Izraeli
Oct 1, 2014·Archives of Pathology & Laboratory Medicine·Melissa Bombery, Jo-Anne Vergilio
Jan 27, 2015·The Journal of Clinical Investigation·Marta Byrska-BishopStella T Chou
Jul 19, 2015·Blood·Tanja A Gruber, James R Downing
Aug 12, 2016·Current Hematologic Malignancy Reports·Neha BhatnagarIrene Roberts
Mar 25, 2017·American Journal of Clinical Pathology·Winston Y LeeGeraldine S Pinkus

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Citations

May 3, 2019·Critical Reviews in Clinical Laboratory Sciences·Valentina SasCiprian Tomuleasa

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