Potential Role of Altered Megakaryocyte CD31 Expression in Myeloproliferative Neoplasms (MPNs)
Amy A Lo, April Chiu, Elizabeth Hyjek, Janet Wilson, Amy Chadburn. Northwestern University, Chicago, IL; Brigham and Women's Hospital, Boston, MA; University of Chicago, Chicago, IL
Background: Progressive fibrosis, which leads to marrow failure in MPNs, correlates with the number of megakaryocytes (MKs), a source of fibrogenic growth factors. Increasing MKs numbers may be due to increased proliferation, decreased apoptosis or accumulation from decreased MK migration and release from the marrow. CD31 is thought to be important in MK trafficking as MKs from CD31 deficient mice and MKs treated with anti-CD31 antibodies exhibit abnormal migration. We correlated CD31 expression by MKs with marrow reticulin fibrosis in patients with primary myelofibrosis (PMF) and polycythemia vera (PV), MPNs most associated with fibrotic marrow failure, to determine if there are CD31 expression abnormalities that correlate with fibrosis.
Design: Spleens from 1 PV and 9 PMF patients (6 male, 4 female, age 18-82) and bone marrow biopsies from 16 PV, 20 PMF (14 male, 22 female, age 33-81) and 14 control patients were immunostained for CD31. Staining for reticulin was performed on bone marrows. CD31 expression pattern and relative number of abnormal staining cells was compared to controls. Degree of abnormality (1-4, 1= normal, 2= 25% abnormal, 3= 50% abnormal, 4=75% abnormal) was correlated with reticulin fibrosis based on WHO criteria.
Results: CD31 was uniformly expressed in the cytoplasm of control MKs with increased intensity at the cell membrane. Bone marrow biopsies and spleens from PV and PMF patients had abnormal CD31 expression in over 75% of MKs (degree 3) with many cases containing atypical MKs with bulbous nuclei completely CD31 negative (41 cases) or lacking expression at the cell membrane (35 cases) and/or around the nucleus (38 cases). Some cases (degree 2) showed “clumpy” cytoplasmic expression. Reticulin staining was increased in PV/PMF patients (average=3) compared to controls (average=0). The PMF/PV cases with grade 4 fibrosis had more MKs lacking CD31 expression or clumpy cytoplasmic positivity.
Conclusions: MKs in PV and PMF exhibit abnormal CD31 expression in the bone marrow and spleen, which correlates with the degree of marrow reticulin fibrosis, suggesting CD31 protein is abnormal, furthering the evidence that CD31 plays a role in the pathogenesis of marrow failure in MPNs. Although the genetic mechanisms underlying these morphologic findings are not known, abnormal CD31 expression by immunohistochemistry may identify patients at increased risk for myelofibrosis.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 221, Wednesday Morning