Spectrin Isoforms Are Useful Markers in Acute Erythroid Leukemia and Acute Megakaryoblastic Leukemia
LR Wolgast, P Bhattacharyya, JZ Gong, C McMahon, J Albanese, S JL, H Ratech. Montefiore Med Ctr, Bronx, NY; Hackensack Univ Med Ctr, Hackensack, NJ; LabCorp of America, Research Triangle Park, NC
Background: Spectrins are a family of large, rod-like, multifunctional molecules involved in cell structure, transmission of signaling and DNA repair. Spectrin gene expression is controlled by the master transcription factor GATA1, which is essential for normal erythropoiesis and megakaryopoiesis. Because little is known about the role of spectrins in leukemogenesis, we studied a comprehensive panel of neoplastic bone marrow disorders.
Design: Using monoclonal antibodies, we immunohistochemically stained bone marrow biopsy tissue sections for αI, αII, βI, and βII spectrin isoforms in normal bone marrow, N=6; myelodysplastic syndrome (MDS), N=5; myeloproliferative neoplasm (MPN), N=20; acute erythroid leukemia (EryL), N=5; and acute megakaryoblastic leukemia (MegL), N=5.
Results: In normal bone marrow, spectrin isoforms were expressed according to cell lineage: αI, βI in erythroid precursors; αII, βII in granulocytic cells; and βI, βII in megakaryocytes (Table 1). There was a normal spectrin pattern for erythroid precursors in MDS and for megakaryocytes in MPN. However, only 2/5 (40%) EryLs expressed both of the αI and βI spectrin isoforms that are normally seen in erythroid precursors. And unlike normal megakaryocytes, which express both βI and βII spectrins, all 5 MegLs expressed βII spectrin, but not βI spectrin (Table 1).
|Granulocytic cell lineage|
|Normal||0/6 (0)||6/6 (100)||0/6 (0)||6/6 (100)|
|MDS||0/5 (0)||4/5 (80)||1/5 (20)||5/5 (100)|
|MPN||0/20 (0)||18/20 (90)||2/20 (10)||20/20 (100)|
|Erythroid cell lineage|
|Normal||6/6 (100)||0/6 (0)||6/6 (100)||0/6 (0)|
|EryL||2/5 (40)||1/5 (20)||3/5 (60)||3/5 (60)|
|Megakaryocytic cell lineage|
|Normal||0/6 (0)||0/6 (0)||6/6 (100)||6/6 (100)|
|MegL||0/5 (0)||0/5 (0)||0/5 (0)||5/5 (100)|