High levels of immunoglobulin expression predict shorter overall survival in patients with acute myeloid leukemia

Abstract

Objectives It has been believed that immunoglobulins can only be produced by B lymphocytes and plasma cells. We have previously reported that IgG can be expressed in myeloblasts from patients with acute myeloid leukemia (AML) and plays a role in the proliferation and apoptosis of leukemic cells. However, its clinical impact has not been assessed. Methods We assessed the expression of different classes of immunoglobulin in peripheral blood and bone marrow samples from 132 AML patients and correlated the levels of expression with clinicopathologic and molecular genetic features, as well as clinical outcome. Results We found that, in addition to IgG, all classes of immunoglobulin are expressed in myeloblasts, including IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. The levels of IgG expression (coupled with Igκ or Igλ) are higher than those of IgM, IgA, IgD, and IgE. Using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with differential expression of immunoglobulin and different clinical outcomes. Conclusions High levels of immunoglobulin expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Assessment of immunoglobulin may serve as a useful marker for prognostic stratification and target therapy.

Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

“…We have detected Igs on the cell surfaces of myeloblasts by multicolor flow cytometry [ 19 ]. High levels of Ig staining signals were associated with poor overall survival.…”

“…We recently reported that detection of a high level of IgG on AML blasts by flow cytometry analysis, coupled with Igκ or Igλ, is associated with poor overall survival [ 19 ]. Considering that AML-derived Ig could not only be on the cell membrane, but may also be located in the cytoplasm or secreted into the circulation, we further assessed AML-derived Ig expression in sorted myeloblasts by qPCR.…”

“…The expression of AML-derived Ig correlated with cell viability, proliferation, and migration [ 16 , 17 , 18 ]. Furthermore, AML patients with blasts showing high levels of IgG staining signals by flow cytometry had significantly poorer overall survival [ 19 ].…”

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

“…Genomic DNA extracted from BM was amplified and subjected to mutation analysis using a panel of 28 ( n = 12 cases) or 81 ( n = 32 cases) genes (commonly mutated in hematopoietic neoplasms) by NGS on an Illumina MiSeq platform (Illumina Inc., San Diego, CA, USA), as described previously [ 9 ].…”

Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

“…The expression of cancer-derived Ig in sarcomas was confirmed in the sarcoma cell lines A673, U-2 OS and HT1080 ( 38 ). In addition, cancer-derived Ig is frequently expressed in acute myeloid leukemia cells ( 39 – 42 ). Thus, cancer-derived Ig is validated to be widely expressed in different cancer lineages, including epithelial cancers, soft tissue tumors, and hematopoietic neoplasms.…”