title: Rearrangement and expression of the immunoglobulin μ-chain gene in human myeloid cells.
abstract: 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 VHμDJHμ 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 VHμDJHμ 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 VHμDJHμ 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.
authors.affiliation: 1] Center for Human Disease Genomics, Peking University, Beijing, China [2] Department of Immunology, School of Basic Medical Sciences, Key laboratory of Immunology, Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Sun
authors.affiliation: 1] Center for Human Disease Genomics, Peking University, Beijing, China [2] Department of Immunology, School of Basic Medical Sciences, Key laboratory of Immunology, Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhiqiao
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pathology, The University of Texas-Medical School, Houston, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: 1] Center for Human Disease Genomics, Peking University, Beijing, China [2] Department of Immunology, School of Basic Medical Sciences, Key laboratory of Immunology, Ministry of Health, Peking University Health Science Center, Beijing, China [3] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D064368:Healthy Volunteers; D006801:Humans; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D016130:Immunophenotyping; D047468:Immunoprecipitation; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D009369:Neoplasms / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger