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
Bloodjournal_title
Bloodauthors
Gurrieri C,Nafa K,Merghoub T,Bernardi R,Capodieci P,Biondi A,Nimer S,Douer D,Cordon-Cardo C,Gallagher R,Pandolfi PPdoi
10.1182/blood-2003-07-2200subject
Has Abstractpub_date
2004-03-15 00:00:00pages
2358-62issue
6eissn
0006-4971issn
1528-0020pii
2003-07-2200journal_volume
103pub_type
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