Regulation of the CD56 promoter and its association with proliferation, anti-apoptosis and clinical factors in multiple myeloma

被引:15
作者
Damgaard, Tina [1 ]
Knudsen, Lene M. [2 ]
Dahl, Inger Marie S. [3 ,4 ]
Gimsing, Peter [2 ]
Lodahl, Marianne [1 ]
Rasmussen, Thomas [1 ]
机构
[1] Herlev Univ Hosp Copenhagen, Dept Haematol 54P4, Herlev, Denmark
[2] Rigshosp, Dept Hematol, DK-2100 Copenhagen O, Denmark
[3] Univ Hosp, Sect Hematol, Tromso, Norway
[4] Univ Tromso, Inst Clin Med, Dept Med, Tromso, Norway
关键词
Multiple myeloma; CD56; transcriptional regulation; proliferation; anti-apoptosis; clinical factors; CELL-ADHESION MOLECULE; MALIGNANT PLASMA-CELLS; HIGH-DOSE CHEMOTHERAPY; MESSENGER-RNA; N-CAM; EXPRESSION; GENE; DYSREGULATION; TRANSLOCATION; FREQUENCY;
D O I
10.1080/10428190802699332
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma (MM) is an incurable B-cell malignancy characterised by uncontrolled growth and accumulation of malignant plasma cells in the bone marrow. Aberrant expression of CD56 in patients with MM is thought to contribute to a worsened disease course and metastasis. We therefore investigated the regulation of the CD56 promoter in relation to typical clinical factors. We used qPCR and FACS to measure the expression levels of CD56, and potential regulatory factors in patients with MM and related these with MM progression/prognosis. The transcription factors BTBD3, Pax5, RUNX1 and MMSET were positively associated with CD56 expression, as was CYCLIN D1, which is involved in disease progression, anti-apoptosis and proliferation. RUNX1 was negatively associated with the survival of stem-cell transplanted patients. Our findings propose four potential activators of the CD56 promoter and for CD56 to be involved in proliferation and anti-apoptosis, leading to disease progression in MM.
引用
收藏
页码:236 / 246
页数:11
相关论文
共 43 条
[1]   Molecular classification of multiple myeloma:: A distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations [J].
Agnelli, L ;
Bicciato, S ;
Mattioli, M ;
Fabris, S ;
Intini, D ;
Verdelli, D ;
Baldini, L ;
Morabito, F ;
Callea, V ;
Lombardi, L ;
Neri, A .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (29) :7296-7306
[2]   Amplification or duplication of chromosome band 21q22 with multiple copies of the AML1 gene and mutation of the TP53 gene in therapy-related MDS and AML [J].
Andersen, MK ;
Christiansen, DH ;
Pedersen-Bjergaard, J .
LEUKEMIA, 2005, 19 (02) :197-200
[3]   EXPRESSION OF ADHESION MOLECULES LFA-3 AND N-CAM ON NORMAL AND MALIGNANT HUMAN PLASMA-CELLS [J].
BARKER, HF ;
HAMILTON, MS ;
BALL, J ;
DREW, M ;
FRANKLIN, IM .
BRITISH JOURNAL OF HAEMATOLOGY, 1992, 81 (03) :331-335
[4]   Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma [J].
Bergsagel, PL ;
Kuehl, WM ;
Zhan, FH ;
Sawyer, J ;
Barlogie, B ;
Shaughnessy, J .
BLOOD, 2005, 106 (01) :296-303
[5]   Chromosome translocations in multiple myeloma [J].
Bergsagel, PL ;
Kuehl, WM .
ONCOGENE, 2001, 20 (40) :5611-5622
[6]   AML1 stimulates G1 to S progression via its transactivation domain [J].
Bernardin, F ;
Friedman, AD .
ONCOGENE, 2002, 21 (20) :3247-3252
[7]   Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma [J].
Borson, ND ;
Lacy, MQ ;
Wettstein, PJ .
BLOOD, 2002, 100 (13) :4629-4639
[8]   The absence of CD56 on malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system [J].
Chang, H ;
Bartlett, ES ;
Patterson, B ;
Chen, CI ;
Yi, QL .
BRITISH JOURNAL OF HAEMATOLOGY, 2005, 129 (04) :539-541
[9]   The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts [J].
Chesi, M ;
Nardini, E ;
Lim, RSC ;
Smith, KD ;
Kuehl, WM ;
Bergsagel, PL .
BLOOD, 1998, 92 (09) :3025-3034
[10]   AYL-1A and AML-1B regulation of MIP-1α expression in multiple myeloma [J].
Choi, SJ ;
Oba, T ;
Callander, NS ;
Jelinek, DF ;
Roodman, GD .
BLOOD, 2003, 101 (10) :3778-3783