TY - JOUR
T1 - IGK with conserved IGKV/IGKJ repertoire is expressed in acute myeloid leukemia and promotes leukemic cell migration
AU - Wang, Chong
AU - Xia, Miaoran
AU - Sun, Xiaoping
AU - He, Zhiqiao
AU - Hu, Fanlei
AU - Chen, Lei
AU - Bueso-Ramos, Carlos E.
AU - Qiu, Xiaoyan
AU - Yin, C. Cameron
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - IgK
KW - Leukemic cell migration
KW - Restricted IGKV/IGKJ rearrangement
KW - Somatic hypermutation
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U2 - 10.18632/oncotarget.5393
DO - 10.18632/oncotarget.5393
M3 - Article
C2 - 26429876
AN - SCOPUS:84948823711
SN - 1949-2553
VL - 6
SP - 39062
EP - 39072
JO - Oncotarget
JF - Oncotarget
IS - 36
ER -