Anaplastic lymphoma kinase proteins and malignancy

被引:30
作者
Pulford, K
Morris, SW
Mason, DY
机构
[1] John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Leukemia Res Fund, Immunodiagnost Unit, Oxford OX3 9DU, England
[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
关键词
D O I
10.1097/00062752-200107000-00009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The anaplastic lymphoma kinase (ALK) gene fuses to the nucleophosmin (NPM) gene as a result of a (2;5) translocation associated with a subtype of human lymphoma (initially designated anaplastic large cell lymphoma [ALCL] or Ki-1/CD30-positive lymphoma). The immunocytochemical detection of NPM-ALK (and proteins encoded by,other ALK fusion genes) has allowed the definition of a tumor entity, "ALK-positive lymphoma" (which shows only partial overlap with pathologists' diagnosis of ALCL), to be defined and is invaluable in distinguishing this disease from ALK-negative large cell lymphomas. Eight variant ALK fusion proteins have been identified. Some are expressed only in ALCL, some are found only in the nonhematopoietic neoplasm inflammatory myofibroblastic tumor (IMT), and some are present in both types of malignancy. The ALK gene is silent in adult tissues except for restricted sites within the nervous system (consequently, patients with ALK-positive lymphoma produce antibodies to the ALK protein) but Is expressed in some neuroblastomas and rhabdomyosarcomas. Biochemical studies suggest an anti-apoptotic function of NPM-ALK, and this may contribute to oncogenesis. Although ALK-positive lymphomas, have a generally good prognosis, new therapeutic regimens are still needed for patients whose disease is refractory to conventional treatment. (C) 2001 Lippincott Williams & Wilkins, Inc.
引用
收藏
页码:231 / 236
页数:6
相关论文
共 48 条
[1]   Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-γ to mediate its mitogenicity [J].
Bai, RY ;
Dieter, P ;
Peschel, C ;
Morris, SW ;
Duyster, J .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (12) :6951-6961
[2]   Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway [J].
Bai, RY ;
Tao, OY ;
Miething, C ;
Morris, SW ;
Peschel, C ;
Duyster, J .
BLOOD, 2000, 96 (13) :4319-4327
[3]   ALK-positive lymphoma:: A single disease with a broad spectrum of morphology [J].
Benharroch, D ;
Meguerian-Bedoyan, Z ;
Lamant, L ;
Amin, C ;
Brugières, L ;
Terrier-Lacombe, MJ ;
Haralambieva, E ;
Pulford, K ;
Pileri, S ;
Morris, SW ;
Mason, DY ;
Delsol, G .
BLOOD, 1998, 91 (06) :2076-2084
[4]  
BRIDGE JA, 2001, IN PRESS AM J PATHOL
[5]   Hypocellular anaplastic large cell lymphoma mimicking inflammatory lesions of lymph nodes [J].
Cheuk, W ;
Hill, RW ;
Bacchi, C ;
Dias, MA ;
Chan, JKC .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2000, 24 (11) :1537-1543
[6]  
COFFIN CM, 2000, LAB INVEST, V80, P8
[7]   ATIC-ALK:: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35) [J].
Colleoni, GWB ;
Bridge, JA ;
Garicochea, B ;
Liu, J ;
Filippa, DA ;
Ladanyi, M .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (03) :781-789
[8]   Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial [J].
Deconinck, E ;
Lamy, T ;
Foussard, C ;
Gaillard, F ;
Delwail, V ;
Colombat, P ;
Casassus, P ;
Lemevel, A ;
Brion, A ;
Milpied, N .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 109 (04) :736-742
[9]   A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2;5 translocation [J].
Delsol, G ;
Lamant, L ;
Mariame, B ;
Pulford, K ;
Dastugue, N ;
Brousset, P ;
RigalHuguet, F ;
AlSaati, T ;
Cerretti, DP ;
Morris, SW ;
Mason, DY .
BLOOD, 1997, 89 (05) :1483-1490
[10]   Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas [J].
Drexler, HG ;
Gignac, SM ;
von Wasielewski, R ;
Werner, M ;
Dirks, WG .
LEUKEMIA, 2000, 14 (09) :1533-1559