Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia

被引:55
|
作者
Gurrieri, C
Nafa, K
Merghoub, T
Bernardi, R
Capodieci, P
Biondi, A
Nimer, S
Douer, D
Cordon-Cardo, C
Gallagher, R
Pandolfi, PP
机构
[1] Cornell Univ, Sloan Kettering Inst, Program Mol Biol,Grad Sch Med Sci, Mem Sloan Kettering Canc Ctr,Dept Pathol, New York, NY 10021 USA
[2] Cornell Univ, Sloan Kettering Inst, Grad Sch Med Sci, Mem Sloan Kettering Canc Ctr,Dept Med, New York, NY 10021 USA
[3] Univ Milano Bicocca, Ctr Ricerca M Tettamanti, Pediat Clin, Monza, Italy
[4] Univ So Calif, Sch Med, Div Hematol, Los Angeles, CA USA
[5] Norris Canc Ctr, Los Angeles, CA USA
[6] Montefiore Med Ctr, New York, NY USA
[7] Albert Einstein Canc Ctr, New York, NY USA
关键词
D O I
10.1182/blood-2003-07-2200
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). In human APL, the dose of PML is reduced to heterozygosity given that one allele is involved in the chromosomal translocation while the status of the remaining PML allele is unknown. We have therefore used single-strand conformational polymorphism (SSCP) and sequencing analysis to screen DNA from APL patients for mutations at the PML locus. We identified DNA sequence variations resulting in a truncated PML protein in APL cases that displayed RA resistance and a very poor prognosis. Mutation analysis also led to the identification of aberrant PML sequence variations in other hematopoietic malignancies. Complete functional loss of PML is therefore selected by the APL phenotype and associates with poor prognosis and RA unresponsiveness. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:2358 / 2362
页数:5
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