TY - JOUR
T1 - Rearrangement and expression of the immunoglobulin μ-chain gene in human myeloid cells
AU - Huang, Jing
AU - Sun, Xiaoping
AU - Gong, Xiaoting
AU - He, Zhiqiao
AU - Chen, Lei
AU - Qiu, Xiaoyan
AU - Cameron Yin, C.
N1 - Funding Information:
This work was supported by a research fund awarded to C C Yin from The University of Texas MD Anderson Cancer Center (#18079170) and a research fund awarded to X Qiu from National Natural Sciences Foundation of China (#81320108020). We thank Markeda Wade from Scientific Publication at The University of Texas MD Anderson Cancer Center for editorial review of the manuscript.
PY - 2014
Y1 - 2014
N2 - Immunoglobulin (Ig), a characteristic marker of B cells, has been reported to be expressed in epithelial cells, with a suggested role in their growth and survival. We have previously reported that IgG heavy chain is expressed in acute myeloid leukemia (AML), but not in the monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. In the present study, we assessed IgM heavy chain expression and repertoire in human myeloid cells. We detected VHμ DJHμ rearrangement and expression in 7/7 AML cell lines, 7/14 primary myeloblasts from AML patients, and interestingly, 8/20 monocytes and 3/20 neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. We also found evidence of somatic hypermutation of the variable (V) gene segments in AML-derived IgM gene rearrangements but not in IgM from monocytes or neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. Furthermore, IgM V Hμ DJHμ gene rearrangements in AML cell lines, primary myeloblasts, and monocytes and neutrophils from patients with non-hematopoietic neoplasms showed a restricted V usage and repertoire, whereas the VHμ DJHμ gene rearrangements in monocytes and neutrophils from healthy individuals displayed more diversity. Anti-human IgM inhibited cell proliferation, but did not induce apoptosis in AML cell lines. Our findings suggest that AML-derived IgM might be a novel AML-related molecule that is involved in leukemogenesis and AML progression and might serve as a useful molecular marker for designing targeted therapy and monitoring minimal residual disease.
AB - Immunoglobulin (Ig), a characteristic marker of B cells, has been reported to be expressed in epithelial cells, with a suggested role in their growth and survival. We have previously reported that IgG heavy chain is expressed in acute myeloid leukemia (AML), but not in the monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. In the present study, we assessed IgM heavy chain expression and repertoire in human myeloid cells. We detected VHμ DJHμ rearrangement and expression in 7/7 AML cell lines, 7/14 primary myeloblasts from AML patients, and interestingly, 8/20 monocytes and 3/20 neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. We also found evidence of somatic hypermutation of the variable (V) gene segments in AML-derived IgM gene rearrangements but not in IgM from monocytes or neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. Furthermore, IgM V Hμ DJHμ gene rearrangements in AML cell lines, primary myeloblasts, and monocytes and neutrophils from patients with non-hematopoietic neoplasms showed a restricted V usage and repertoire, whereas the VHμ DJHμ gene rearrangements in monocytes and neutrophils from healthy individuals displayed more diversity. Anti-human IgM inhibited cell proliferation, but did not induce apoptosis in AML cell lines. Our findings suggest that AML-derived IgM might be a novel AML-related molecule that is involved in leukemogenesis and AML progression and might serve as a useful molecular marker for designing targeted therapy and monitoring minimal residual disease.
KW - Acute myeloid leukemia
KW - IgM
KW - VDJ gene rearrangements
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U2 - 10.1038/cmi.2013.45
DO - 10.1038/cmi.2013.45
M3 - Article
C2 - 24141767
AN - SCOPUS:84891815704
SN - 1672-7681
VL - 11
SP - 94
EP - 104
JO - Cellular and Molecular Immunology
JF - Cellular and Molecular Immunology
IS - 1
ER -