Mendelian randomization analysis reveals the causal relationship between immune cells and leukemia.

Background: Increasing evidence indicates certain types of immune cells are linked to leukemia, but whether this link is causal has remained unclear.

Methods: A two-sample Mendelian randomization (MR) analysis was conducted to examine the causal relationship (CR) among 731 immune cell traits and leukemia. The inverse variance weighted (IVW) technique was applied, along with the weighted median and MR-Egger approaches, to analyze the data. The instrumental variables were validated for heterogeneity and pleiotropy using sensitivity analyses.

Results: A total of 58 immune cell traits with CRs with leukemia were identified, of which 15 were considered risk factors for leukemia. The factors were distributed among acute myeloid leukemia (AML) (3 traits), acute lymphoblastic leukemia (ALL) (4 traits), chronic myeloid leukemia (CML) (3 traits), and chronic lymphocytic leukemia (CLL) (5 traits). Additionally, 43 immune traits were considered protective factors for leukemia and were distributed among ALL (15 traits), AML (9 traits), CLL (18 traits), and CML (1 trait). After FDR correction, it was found that terminally differentiated CD4 + T cell absolute count is a protective factor for CLL. Immune traits with CRs between both types of leukemia included "CD62L-plasmacytoid dendritic cell %," "plasmacytoid dendritic cell absolute count," "CD11c on granulocytes," "HLA DR + CD8 + T cell %lymphocytes," "HLA DR + CD8 + T cell %," "HLA DR + T cell %," "CD28 on CD28 + CD45RA + CD8 + T cells," "HLA DR + CD4 + T cell absolute count," and "CD45RA- CD28- CD8 + T cell absolute count."

Conclusions: The results of this investigation reveal that leukemia closely relates to specific types of immune cells. Our findings provide a scientific basis for further investigations into factors that will improve immunotherapy.