Association of promyelocytic leukemia protein with expression of IL-6 and resistance to treatment in multiple myeloma.
OBJECTIVE
Promyelocytic leukemia protein (PML) was originally identified as a tumor suppressor but has been recently shown to have the ability to control stem cell function in multiple tissues including malignancies. This study aimed to evaluate the biological and clinical significance of PML in multiple myeloma (MM).


METHODS
We knocked down PML in myeloma cells with a lentiviral vector expressing microRNA to target PML, which were used for in vitro analyses. We also evaluated the association between PML expression in the bone marrow and patients' clinical parameters.


RESULTS
The expression of IL-6 was decreased in myeloma cells with knocked-down PML expression. Immunohistochemical study showed that the PML expression level varied widely in the bone marrow of 48 MM patients, and that IL-6 expression correlated with PML expression in these patients. In addition, MM with high PML expression at diagnosis showed a poor prognosis regarding the 2-year survival, and PML and IL-6 positivity increased with the progression of disease in 13 sequentially analyzed cases.


CONCLUSIONS
These results suggest that PML expression was positively associated with IL-6 expression in patients and was also related to tumor development and resistance to treatment in MM.
Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Daisuke
D
Ohgiya
Hiromichi
H
Matsushita
Makoto
M
Onizuka
Naoya
N
Nakamura
Jun
J
Amaki
Yasuyuki
Y
Aoyama
Hidetsugu
H
Kawai
Yoshiaki
Y
Ogawa
Hiroshi
H
Kawada
Kiyoshi
K
Ando
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D015850:Interleukin-6; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human