MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.
Ito
Masato
M
Second Department of Internal Medicine, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601.
Iida
Shinsuke
S
Inagaki
Hiroshi
H
Tsuboi
Kazuya
K
Komatsu
Hirokazu
H
Yamaguchi
Motoko
M
Nakamura
Naoya
N
Suzuki
Ritsuro
R
Seto
Masao
M
Nakamura
Shigeo
S
Morishima
Yasuo
Y
Ueda
Ryuzo
R
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D000090266:Chromobox Protein Homolog 5; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D000099218:Interferon Regulatory Factor-4
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000090266:Chromobox Protein Homolog 5; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C000715594:CBX5 protein, human; C498154:CD38 protein, human