the Difference In Protein Profiles Of B Cells And T Cells Between Aplastic Anemia And Myelodysplastic Syndrome Patients

Open Access
Miller, Elizabeth Lauren
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Jeffrey J Pu, Thesis Supervisor
  • Dr. Ronald Walker, Honors Advisor
  • Sairam V Rudrabhatla, Faculty Reader
  • Myelodysplastic syndrome
  • Aplastic Anemia
  • Protein
  • B lymphocytes
Aplastic anemia (AA) and hypocellular myelodysplastic syndrome (MDS) are two common acquired bone marrow failure diseases. AA is mostly an acquired bone marrow disease caused by cellular and humoral mediated immune attack of hematopoietic stem cells (HSC) due to dysregulation of immune system, which leads to hematopoietic stem cell and progenitor cell immaturely apoptosis and bone marrow failure. MDS is a group of acquired heterogeneously clonal HSC disorders with ineffective hematopoiesis. Approximately 10% to 20% of MDS manifests a reduced bone marrow cellularity, which comprises hypocellular MDS. There is increased experimental and clinical data indicating that an immune-mediated insult to hematopoietic HSCs and changes in the hematopoiesis-supporting microenvironment contribute to the pathogenesis of hypocellular MDS. Because of the similarity of their bone marrow manifestation, hypocellular MDS and AA are often hard to distinguish. Mounting evidence indicates that abnormal activation of cytotoxic T cells plays a crucial role in the pathophysiology of these diseases. However the difference in immune dysregulation in these two diseases, especially the role of B lymphocyte population, has not been thoroughly studied. Our study aims to find unique B lymphocyte surface marker expression patterns of hypocellular MDS and AA to help us understanding the pathogeneses of these two diseases. This study retrospectively analyzed flow cytometry lymphocytic antigen expression profiles from patients diagnosed as AA and hypocellular MDS as per standard criteria. A total of 31 AA and 26 hypocellular MDS patient cases were recruited. The bone marrow aspirate/biopsy data, bone marrow aspiration flow cytometry reports, and Complete Blood Counts (CBC)s from individual patients were analyzed. Using side scatter (SSC) vs. CD45 gating flow cytometry panels, we identified immature cell population (SSClow/CD45low) and lymphocyte population (SSClow/CD45high). We then quantitatively analyzed the expression patterns of 33 cluster differentiation (CD) molecules on individual sample. Finally, we compared the CD expression patterns between AA and hypocellular MDS in both cell populations respectively. We found that CD19 expression was significantly higher in AA than in hypocellular MDS in both SSClow/CD45low cell population (P=0.001) and SSClow/CD45high cell population (P=0.003). Hypocellular MDS contains significantly higher CD34high cells than AA in SSClow/CD45low populations (mean:28.5% vs 8.5%; range; 1% to 94% vs 2% to 27%; P=0.04). However, patients with both diseases similarly contains very few CD34high cells in SSClow/CD45high cell population (mean: 0.6% vs 2.6%; range: 0.0% to 2% vs 0.0% to 32%; P=0.99). This study showed that B cells are highly proliferative in both immature stage and mature stage in AA but not in hypocellular MDS; the majority of lymphocyte population are mature cells in both AA and hypocellular MDS. These data indicates that B cells may play a unique role in AA pathogenesis but not in hypocellular MDS; the pathogeneses of both diseases caused by a persistently dysregulated immune microenvironment, not by an acute insult; and CD19 expression pattern may be a useful marker to distinguish AA and hypocellular MDS.