Analysis of Clinical Characteristics and Pathogenic Mechanisms of Non-Severe Aplastic Anemia Associated with Active Sternum Bone Marrow Hyperplasia

Keywords: Non-severe aplastic anemia, bone marrow hyperplasia, B lymphocyte

Methods: A total of 72 AA patients were included in this study, including 39 NSAA patients and 33 SAA patients. 33 patients with NSAA had active sternal bone marrow hyperplasia and 6 patients had NSAA with reduced proliferation in the sternum and iliac bone (this number was too small to be included in the statistical analysis). According to whether the sternum bone marrow hyperplasia is active or not ,we divided these 33 patients into NSAA-hyper group and NSAA-hypo group.

Results: The pretreatment blood analysis revealed that the NSAA-hyper group had a higher peripheral blood hemoglobin level, platelet level, reticulocyte percentage, and reticulocyte count than those of the SAA-hyper group. Additionally, the NSAA-hyper group had a higher white blood cell count, ANC, neutrophil percentage, reticulocyte percentage, and reticulocyte count than those of the SAA-hypo group. Moreover, the proportion of red blood cells in the iliac bone marrow and the number of megakaryocytes in the sternal bone marrow of the NSAA-hyper group were higher than those of the SAA-hyper group. Additionally, the proportions of granulocytes and red blood cells and the number of megakaryocytes in the iliac and sternal bone marrow of the NSAA-hyper group were higher than those of the SAA-hypo group. The pretreatment ANC and neutrophil percentage in the peripheral blood of the SAA-hyper group were higher than those of the SAA-hypo group. The proportions of granulocytes in the iliac and sternal bone marrow were similar in the SAA-hyper and SAA-hypo groups. The ORR of the SAA-hyper group with active sternal proliferation (69.20%) was higher than that of the SAA-hypo group (30%). Our analysis validated that the degree of reduction in the peripheral blood cell count and bone marrow damage were less severe in the SAA-hyper group than they were in the SAA-hypo group. Patients in the NSAA-hyper group had a higher ORR (complete response [CR]+partial response [PR]=75.8%) than that of patients in the SAA-hyper group (CR+PR=69.2%); furthermore, patients in the NSAA-hyper group experienced a significant increase in the ORR compared to that of patients in the SAA-hypo group (CR+PR=30.0%).Active sternal hyperplasia may be a valid indicator of the overall treatment efficacy.

We noticed that the proportion of CD19⁺ B lymphocytes was increased in some patients with NSAA. Based on the average proportion of CD19⁺ B cells of the healthy controls, we divided patients with an increased percentage of CD19⁺ B lymphocytes into the NSAA-hyper1 group and patients with a decreased percentage of CD19⁺ B lymphocytes into the NSAA-hyper2 group for further analyses. We found that the peripheral blood neutrophil percentage of patients in the NSAA-hyper1 group was higher than that of those in the NSAA-hyper2 group. The proportion of plasma cells in the iliac bone marrow of the NSAA-hyper1 group was higher than that of the NSAA-hyper2 group. The efficacy evaluation revealed that the ORR of patients in the NSAA-hyper1 group (CR+PR=84.20%) was higher than that of those in the NSAA-hyper2 group (CR+PR=64.30%).

Therefore, we performed a proteomic analysis to study the differences in the CD19⁺ B cell protein composition observed in patients with NSAA with increased B cells and healthy controls. The preliminary findings revealed that differentially expressed proteins such as HLA-DQB1, CDK6 and CEACAM1 were highly expressed in patients with NSAA, thus promoting the development, activation, and proliferation of B lymphocytes in the disease state. Concurrently, high-level expressions of IgM, IgG1, and IgG3 were associated with the involvement of B cells in humoral immune regulation. In the complement regulatory system, the expression of C1qrs was reduced, whereas the expressions of C3, C4, C4BP, C6, C7, C8, C9, CR1, CR3, and CR4 were increased. Therefore, we speculated that the complement pathway may be involved in the regulation of the B-cell function, thereby affecting the pathogenesis of AA.

Conclusion: Our study results indicated that active bone marrow proliferation in the sternum can be an important indicator of a favorable prognosis for patients with AA. Additionally, B cells may play an essential role in regulating the immune status of AA.

No relevant conflicts of interest to declare.