IGK with conserved IGΚV/IGΚJ repertoire is expressed in acute myeloid leukemia and promotes leukemic cell migration
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Chong Wang1,*, Miaoran Xia1,2,*, Xiaoping Sun3, Zhiqiao He2, Fanlei Hu1, Lei Chen4, Carlos E. Bueso-Ramos2, Xiaoyan Qiu1,2,*, C. Cameron Yin2,*
1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China
2Department of Hematopathology, UT MD Anderson Cancer Center, Houston, TX, USA
3Department of Laboratory Medicine, UT MD Anderson Cancer Center, Houston, TX, USA
4Department of Pathology, University of Texas-Houston Medical School, Houston, TX, USA
*CW and MX contributed equally to this work. XQ and CCY contributed equally to this work.
C. Cameron Yin, e-mail: [email protected]
Xiaoyan Qiu, e-mail: [email protected]
Keywords: IgK, acute myeloid leukemia, restricted IGKV/IGKJ rearrangement, somatic hypermutation, leukemic cell migration
Received: July 20, 2015 Accepted: September 17, 2015 Published: September 29, 2015
We have previously reported that immunoglobulin heavy chain genes were expressed in myeloblasts and mature myeloid cells. In this study, we further demonstrated that rearranged Ig κ light chain was also frequently expressed in acute myeloid leukemia cell lines (6/6), primary myeloblasts from patients with acute myeloid leukemia (17/18), and mature monocytes (11/12) and neutrophils (3/12) from patients with non-hematopoietic neoplasms, but not or only rarely expressed in mature neutrophils (0/8) or monocytes (1/8) from healthy individuals. Interestingly, myeloblasts and mature monocytes/neutrophils shared several restricted IGKV and IGKJ gene usages but with different expression frequency. Surprisingly, almost all of the acute myeloid leukemia-derived IGKV showed somatic hypermutation; in contrast, mature myeloid cells-derived IGKV rarely had somatic hypermutation. More importantly, although IGK expression appeared not to affect cell proliferation, reduced IGK expression led to a decrease in cell migration in acute myeloid leukemia cell lines HL-60 and NB4, whereas increased IGK expression promoted their motility. In summary, IGK is expressed in myeloblasts and mature myeloid cells from patients with non-hematopoietic neoplasms, and is involved in cell migration. These results suggest that myeloid cells-derived IgK may have a role in leukemogenesis and may serve as a novel tumor marker for monitoring minimal residual disease and developing target therapy.
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