The biological and clinical significance of MLL abnormalities in haematological malignancies

被引:30
作者
Mitterbauer-Hohendanner, G [1 ]
Mannhalter, C [1 ]
机构
[1] Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria
关键词
acute leukaemia; chromosome; 11q23; classification of leukaemias; leukaemogenesis; MLL gene;
D O I
10.1111/j.0960-135X.2004.01366.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The MLL ((M) under bar ixed (L) under bar ineage (L) under bar eukaemia or (M) under bar yeloid/(L) under bar ymphoid (L) under bar eukaemia) gene on chromosome 11q23 is frequently involved in chromosomal translocations associated with human acute leukaemias. These translocations lead to fusion genes generally resulting in novel chimeric proteins containing the amino terminus of MLL fused in-frame to one of about 30 distinct partner proteins. Abnormalities involving the MLL gene are observed in leukaemias of either lymphoid or myeloid lineage derivation, as well as in poorly differentiated or biphenotypic leukaemias. They are frequently seen in infant patients, and patients with therapy-related secondary AML following treatment with inhibitors of topoisomerase II (epipodophyllotoxins). In the majority of cases, abnormalities involving the MLL gene are associated with a very poor prognostic outcome. In this review, we will discuss some of the recent advances in MLL research resulting from biological as well as clinical studies.
引用
收藏
页码:12 / 24
页数:13
相关论文
共 139 条
[11]   Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: Correlation with scaffold attachment regions and topoisomerase II consensus binding sites [J].
Broeker, PLS ;
Super, HG ;
Thirman, MJ ;
Pomykala, H ;
Yonebayashi, Y ;
Tanabe, S ;
ZeleznikLe, N ;
Rowley, JD .
BLOOD, 1996, 87 (05) :1912-1922
[12]   The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures [J].
Butler, LH ;
Slany, R ;
Cui, XM ;
Cleary, ML ;
Mason, DY .
BLOOD, 1997, 89 (09) :3361-3370
[13]   The partial tandem duplication of ALL1 in acute myeloid leukemia with normal cytogenetics or trisomy 11 is restricted to one chromosome [J].
Caligiuri, MA ;
Strout, MP ;
Oberkircher, AR ;
Yu, F ;
delaChapelle, A ;
Bloomfield, CD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3899-3902
[14]  
Caligiuri MA, 1998, CANCER RES, V58, P55
[15]   A NOVEL CLASS OF ZINC-FINGER LEUCINE-ZIPPER GENES IDENTIFIED FROM THE MOLECULAR-CLONING OF THE T(10-11) TRANSLOCATION IN ACUTE-LEUKEMIA [J].
CHAPLIN, T ;
AYTON, P ;
BERNARD, OA ;
SAHA, V ;
DELLAVALLE, V ;
HILLION, J ;
GREGORINI, A ;
LILLINGTON, D ;
BERGER, R ;
YOUNG, BD .
BLOOD, 1995, 85 (06) :1435-1441
[16]  
CHERIF D, 1994, LEUKEMIA, V8, P578
[17]   Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999 [J].
Chessells, JM ;
Harrison, CJ ;
Watson, SL ;
Vora, AJ ;
Richards, SM .
BRITISH JOURNAL OF HAEMATOLOGY, 2002, 117 (02) :306-314
[18]   A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15 [J].
Chinwalla, V ;
Chien, A ;
Odero, M ;
Neilly, MB ;
Zeleznik-Le, NJ ;
Rowley, JD .
ONCOGENE, 2003, 22 (09) :1400-1410
[19]  
CIMINO G, 1995, CANCER RES, V55, P1625
[20]   Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study:: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome [J].
Cimino, G ;
Elia, L ;
Mancini, M ;
Annino, L ;
Anaclerico, B ;
Fazi, P ;
Vitale, A ;
Specchia, G ;
Di Raimondo, F ;
Recchia, A ;
Cuneo, A ;
Mecucci, C ;
Pane, F ;
Saglio, G ;
Foà, R ;
Mandelli, F .
BLOOD, 2003, 102 (06) :2014-2020