MicroRNAs in Acute Myeloid Leukemia and Other Blood Disorders

Abstract

Common blood disorders include hematopoietic cell malignancies or leukemias and plasma cell dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several leukemias including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) and identify altered microRNAs and their targets. Immune disorders with altered blood levels of antibodies include autoimmune disorders, such as systemic lupus erythematosus (SLE) with associated anti-self-autoantibodies and immunoglobulin A nephropathy (IgAN) also have related microRNA abnormalities. The alterations in microRNAs may serve as therapeutic targets in these blood disorders.

Figure 1

Schematic mechanism of miR-15/107 family alterations in hematopoietic disorders. Decreased expression of miR-15/107 family members is found in malignant cells from AML (acute myeloid leukemia), CLL (chronic lymphocytic leukemia), and MM (multiple myeloma) patients. The underexpression of miR-15/107 may also contribute to increased immunosuppressive regulatory B (Breg) and T cells (Treg), which further promote the expansion and survival of malignant cells. In contrast, with increased miR-15/107, there may be a loss of immunosuppression that leads to SLE (systemic lupus erythematosus) development and antitumor responses. In the therapeutically induced differentiated AML cells, and terminally differentiated B cells, plasma cells (with decreased B-cell-specific activator protein (BSAP), the negative regulator of miR-15a/16-1), miR-15/107 family members would be upregulated, leading to the loss of malignant potential and an increase in differentiation function (SLE).