[1468] Acute Myeloid Leukemias Frequently Lose Expression of αII Spectrin and/or Gain Expression of βI Spectrin Isoforms

LR Wolgast, L Cannizzaro, K Ramesh, X Xue, D Wang, C McMahon, J Albanese, JL Sunkara, H Ratech. Montefiore Medical Center, Bronx, NY; Albert Einstein College of Medicine, Bronx, NY

Background: Spectrins are a family of large, rod-like, multifunctional molecules involved in cell structure, transmission of signaling and DNA repair. Loss of αII spectrin has been implicated in the pathogenesis of Fanconi anemia, a genetic disorder with a predisposition to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The role of spectrin isoforms is poorly understood in normal hematopoiesis and in leukemogenesis. Therefore, we studied a comprehensive panel of AMLs with well-characterized cytogenetic abnormalities.
Design: We immunohistochemically stained bone marrow biopsy tissue sections for αI, αII, βI, and βII spectrin isoforms in reactive bone marrow, N=6, and in 41 cytogenetically-characterized AMLs: t(8;21), N=8; inv(16), N=4; t(15;17), N=5; 11q23, N=2; MDS transformed to AML (MDS→AML), N= 13; chronic myeloid leukemia in blast crisis (CML-BC), N=3; and cytogenetically normal (CN)-AML, N=6. We defined positive staining for a particular spectrin isoform as expression by at least 20% of the cells.
Results: In reactive bone marrow, spectrin isoforms were differentially expressed according to cell lineage: αI, βI in erythroid precursors; αII, βII in granulocytic lineage; and βI, βII in megakaryocytes. At all stages of maturation, the normal granulocytic cell lineage was positive for αII spectrin and negative for βI spectrin. In contrast, a large proportion of AMLs (17/41, 41%) lacked αII spectrin and/or aberrantly expressed βI spectrin isoforms (Table 1; p=0.0145, Fisher's exact test).

Table 1: Spectrin Isoforms in AML

Cytogenetic category	Cases with abnormal spectrin*/Total cases	Percent
inv(16)	4/4	100
11q23	2/2	100
t(15;17)	3/5	60
CN-AML	3/6	50
MDS→AML	4/13	31
t(8;21)	1/8	13
CML-BC	0/3	0
TOTAL:	17/41	41

*Loss of αII spectrin and/or gain of βI spectrin isoforms.


Conclusions: Our data show frequent loss and/or gain of spectrin isoforms in 41% of AMLs tested. We believe that this is highly suggestive of a heretofore-unsuspected connection between spectrin expression and leukemogenesis. However, additional studies are needed to formally distinguish between a driver versus a passenger role for spectrins in AML.
Category: Hematopathology

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 170, Tuesday Afternoon