Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Gurrieri C,Nafa K,Merghoub T,Bernardi R,Capodieci P,Biondi A,Nimer S,Douer D,Cordon-Cardo C,Gallagher R,Pandolfi PP

doi

10.1182/blood-2003-07-2200

subject

Has Abstract

pub_date

2004-03-15 00:00:00

pages

2358-62

issue

6

eissn

0006-4971

issn

1528-0020

pii

2003-07-2200

journal_volume

103

pub_type

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