Among patients with acute myeloid leukemia (AML), high levels of immunoglobulin (Ig) expression are linked to monocytic differentiation, multilineage, dysplasia, gene mutations, and worse overall survival, according to study results published in the European Journal of Haematology.
A team of investigators conducted a study to compare the expression of various Ig classes in peripheral blood and bone marrow of patients with AML, and to analyze how these expressions may affect clinicopathologic features, molecular genetic features, and clinical outcomes.
In previous studies, the investigators found that, in patients with AML, IgG can be expressed by myeloblasts, which can influence proliferative and apoptotic outcomes in leukemic cells. In an effort to assess the clinical implications of this, the authors collected blood and marrow samples from 132 patients with AML (73 men, median age at diagnosis 65.5 years) to measure the myeloblast surface expression of IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. All patients were treated with multiagent chemotherapy and 37 patients received allogeneic stem cell transplantation.
Of the cohort, 48% presented with leukocytosis, 35% presented with leukopenia, 95% presented with anemia, and 73% presented with thrombocytopenia. In addition, 33% of patients had monocytosis, 59% of patients had elevated levels of serum lactate dehydrogenase, and 58% of patients had elevated levels of β2-microglobulin.
During the median follow-up of 16 months, 103 patients died, 8 patients had persistent disease, and 21 patients reached complete remission.
Coupled with Igκ and Igλ, IgG expression levels were higher than IgM, IgA, IgD and IgE; 125 patients had available IgG data and were sorted into high-expression (30%) and low-expression (70%) groups. High-expression group patients had higher white blood cell counts (P =.02), more monocytic differentiation in blasts (P =.001), and dysplasia (P <.001) compared with low-expression group patients.
In addition, the authors analyzed the relationship between levels of Igκ, Igλ, and IgG expression and found that higher levels of Ig expression were linked to several gene mutations, including TET2 and KRAS, and significantly shorter overall survival.
“These findings suggest that AML-derived [Ig] has a role in AML pathogenesis, and may contribute, at least in part, to its correlation with poor clinical outcome,” the authors noted.
The authors concluded that their findings reveal the assessment of immunoglobulin expression may be a useful marker for stratifying prognosis and for the development of targeted therapy.
Wu L, Xia M, Sun X, et al. High levels of immunoglobulin expression predict shorter overall survival in patients with acute myeloid leukemia [published online June 14, 2020]. Eur J Haematol. doi: 10.1111/ejh.13466