Mature Megakaryocytes Display High-Level CD34 Expression in a Subset of Patients with Myeloma Precursor Disease
Irina Maric, Qing Yan Liu, Neha Korde, Olga Simakova, Katherine Calvo, Adriana Zingone, Rene Costello, Mary Ann Yancey, Prashant Tembhare, Constance Yuan, Maryalice Stetler-Stevenson, Ola Landgren. NIH, CC, Bethesda, MD; NIH, Bethesda, MD
Background: For more than four decades, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been reported following multiple myeloma (MM). Treatment-related factors have been considered to be the main cause of the observed elevated risk. Recently, we found an excess risk for AML/MDS in IgG/IgA MGUS, supporting a role for non-treatment related factors in disease development. To follow-up on our findings, we conducted histomorphological analysis of bone marrow (BM) biopsies from MGUS and smoldering myeloma (SMM) patients with the aim to identify early signs of asynchronous/dyspoietic maturation of hematopoietic precursors.
Design: A total of 80 MGUS/SMM patients diagnosed by WHO criteria were enrolled in this interim analysis of our prospective natural history study of myeloma precursor disease. All BM biopsies were performed at baseline. We performed morphologic analysis, reticulin staining and CD34 immunohistochemistry on all cases.
Results: We found 16 patients (20%) (7 MGUS and 9 SMM) with aberrant high-level CD34 expression on mature megakaryocytes (defined as >20% of megakaryocytes in the BM showing membranous/Golgi staining). Patient's median age was 59 yrs (range 45-79 yrs), median fraction of plasma cells in bone marrows was 9.8% (range 5-20%); M-spike concentrations was 0.95 g/dL (range 0.1-2.1 g/dL); peripheral blood counts showed no significant cytopenias. Morphologic analysis showed that CD34(+) cases had more small, hypolobated megakaryocytes (100% vs. 43%; p=0.05) than controls. There was no significant dysgranulopoiesis and dyserythropoiesis. There were no significant differences in fibrosis by reticulin staining. CD34 (+) cases showed higher BM cellularity (48% vs. 38%; p=0.006) and higher myeloblast numbers (2.8% vs. 1.4%; p=0.005) than controls. Interestingly, predominance of erythroid precursors (reversed M:E ratio) was present in 6/14 (43%) of controls and 0/16 (0%) of CD34 (+) cases (p=0.005), suggesting possible differential regulation of myeloid and erythroid hematopoiesis in these two groups.
Conclusions: Recent studies suggested that high-level CD34 expression on mature megakaryocytes may favor diagnosis of MDS, and poor outcome in patients with established MDS diagnosis. In this context, our novel results show that a subpopulation of MGUS/SMM patients (∼20%) have atypical hematopoiesis, particularly megakaryopoiesis, suggesting that non-treatment related factors may play a role in development of MDS/AML following MM.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 231, Wednesday Afternoon