The Specificity of Immunophenotypic Alterations in Blasts in Non-Acute Myeloid Disorders
AM Harrington, H Olteanu, SH Kroft. Medical College of Wisconsin, Milwaukee, WI
Background: Existing data regarding flow cytometric (FC) abnormalities in non-acute myeloid disorders is confounded by variable gating strategies and control groups generally limited to normal bone marrows (BMs). CD45/side scatter gating, the most common approach to blast isolation, is imprecise, with blasts typically representing a minority of gated events. Using an approach designed to delineate all relevant BM populations, we sought to precisely isolate and immunophenotypically characterize blasts in MDS, MPD, and CMML. We compared the findings to both normal BMs and non-neoplastic cytopenias and cytoses, in order to determine the specificity of the immunophenotypic (IP) changes.
Design: Diagnostic BMs of 16 MDSs, 12 MPDs, and 7 CMMLs were compared to 20 non-neoplastic cytopenias/cytoses (CCs) and 10 (-) lymphoma staging BMs, using cluster analysis of 4-color FC tubes designed to delineate all relevant populations using the following antigens: CD7, CD10, CD11b, CD13, CD14, CD15, CD16, CD20, CD22, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, and HLA-DR. Blasts were recognized as distinct clusters, after exclusion of all other populations. Antigen alterations were defined as at least a half-log shift.
Results: Blasts in 10/20 CCs (50%) showed IP differences (1-2/case) vs controls, including over- and underexpression of CD13 and CD117, overexpression of HLA-DR, and variability in CD33 and CD38. IP alterations were identified in 12/16 (75%) MDSs , 9/12 (75%) MPDs, and 7/7 (100%) CMMLs vs controls, and 8/16 (50%) MDSs, 5/12 (41.7%) MPDs, and 3/7 (42.9%) CMMLs compared to CCs. There were 1-4 changes/case in MDSs, 1-3/case in CMMLs, and 1-2/case in MPDs. IP changes exclusive to neoplastic blasts included expression of CD7 (3/16 MDSs, 4/12 MPDs, 1/7 CMMLs), CD15 (1/16 MDSs, 1/7 CMMLs), CD16 (1/16 MDSs), CD36 (1/16 MDSs), CD56 (1/16 MDSs, 1/7 CMMLs), and CD64 (1/16 MDSs, 1/7 CMMLs); variable HLA-DR (3/16 MDSs, 1/12 MPDs, 2/7 CMMLs); underexpression of CD33 (3/16 MDSs), CD38 (1/16 MDSs), and CD45 (3/16 MDSs, 1/12 MPDs, 1/7 CMMLs); and partial loss of CD117 (1/12 MPDs). In all cases, the entire blast population was CD34(+).
Conclusions: Several blast IP alterations were seen in both non-acute myeloid malignancies and non-neoplastic cytopenias and cytoses and are therefore not neoplasia-specific. Approximately 40-50% of MDSs, MPDs, and CMMLs exhibited aberrancies not seen in reactive BMs, including expression of CD7 and CD56, variability of HLA-DR, and underexpression of CD33 and CD45. Of note, the entire blast population was CD34 (+) in all neoplastic cases.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 196, Wednesday Afternoon