IGK with conserved IGKV/IGKJ repertoire is expressed in acute myeloid leukemia and promotes leukemic cell migration

// Chong Wang 1, * , Miaoran Xia 1, 2, * , Xiaoping Sun 3 , Zhiqiao He 2 , Fanlei Hu 1 , Lei Chen 4 , Carlos E. Bueso-Ramos 2 , Xiaoyan Qiu 1, 2, * , C. Cameron Yin 2, * 1 Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China 2 Department of Hematopathology, UT MD Anderson Cancer Center, Houston, TX, USA 3 Department of Laboratory Medicine, UT MD Anderson Cancer Center, Houston, TX, USA 4 Department 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. Correspondence to: C. Cameron Yin, e-mail: cyin@mdanderson.org Xiaoyan Qiu, e-mail: qiuxy@bjmu.edu.cn 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 ABSTRACT 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.