Blood and Bone Marrow Myeloblasts Show Immunophenotypic Variation in Cases of Acute Lymphoblastic Leukemia
Fernando J Castro-Silva, Nitin J Karandikar, Franklin S Fuda, Brian M Levenson. UT Southwestern, Dallas, TX
Background: Identifying immunophenotypic (IP) aberrations in myeloid progenitor cells (MPC) by flow cytometry (FC) is often integral to the diagnosis of clonal myeloid disorders such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or acute myeloid leukemia (AML). However, IP aberrations are not specific for myeloid neoplasms and may be encountered in non-neoplastic conditions. We sought to identify IP variations in MPC from patients at the time of diagnosis of acute lymphoblastic leukemia (ALL).
Design: We searched our FC database to identify new diagnoses of B or T ALL rendered between 2007 and 2011. Mixed phenotype acute leukemias and blast crises of previously diagnosed MPN were excluded. The FC IP of MPC was evaluated in each case using a panel of more than 25 lymphoid and myeloid antigens with cluster analysis of ungated data. Using a combination of antibodies to CD13, CD15, CD33, CD34, CD38, CD45, CD117 and HLA-DR, MPC were identified and enumerated based on their staining pattern and light scatter characteristics. The IP of MPC was then compared to a control population of negative bone marrows (BM) acquired for lymphoma staging or plasma cell neoplasm assessment.
Results: A total of 150 patients newly diagnosed with ALL by FC were identified, including 100 BM and 50 peripheral blood (PB) specimens. BM MPC represented 0.01% to 2.3% of cells (mean=0.19%), which was significantly lower than controls (mean=0.88%, p<0.05). PB MPC ranged from 0.03% to 1.2% (mean=0.33%). Compared to controls, BM MPC included fewer CD38-expressing cells (92% vs 98%, p<0.05), dimmer and more variable CD38 expression (mean MFI 676 vs 1324, p<0.05; MFI CV 110 vs 71, p<0.05), dimmer CD33 expression (mean MFI 101 vs 147, p<0.05), and brighter CD34 expression (mean MFI 1099 vs 97, p<0.05). PB MPC included fewer CD33-expressing cells (67% vs 88%, p<0.05), fewer CD38-expressing cells (91% vs 98%, p<0.05), more variable CD33 expression (MFI CV 144 vs 101, p<0.05), brighter CD34 expression (mean MFI 1008 vs 97, p<0.05), dimmer and more variable CD38 expression (mean MFI 308 vs 1324, p<0.05; MFI CV 118 vs 71), and more variable HLA-DR expression (MFI CV 109 vs 87, p<0.05).
Conclusions: MPC isolated from PB or BM of patients newly diagnosed with ALL frequently exhibit IP variation, particularly in CD33, CD34, CD38, and HLA-DR expression. Bright CD34 expression and dimmer CD38 expression by MPC in ALL suggests an expansion of a more primitive stem cell. Our findings suggest that these specific aberrations may be less informative in follow up cases post-ALL therapy, where MDS or evolving AML may be suspected.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 236, Wednesday Morning