Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia Journal Article


Authors: Gurrieri, C.; Nafa, K.; Merghoub, T.; Bernardi, R.; Capodieci, P.; Biondi, A.; Nimer, S.; Douer, D.; Cordon-Cardo, C.; Gallagher, R.; Pandolfi, P. P.
Article Title: 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 hematopoletic malignancies. Complete functional loss of PML is therefore selected by the APL phenotype and associates with poor prognosis and RA unresponsiveness. © 2004 by The American Society of Hematology.
Keywords: child; controlled study; gene mutation; gene sequence; major clinical study; sequence analysis; drug activity; antineoplastic agents; cytarabine; phenotype; animals; mice; allele; cells, cultured; apoptosis; neoplasm proteins; gene function; drug resistance, neoplasm; mutational analysis; transcription factors; nuclear proteins; tumor suppressor gene; leukemia, promyelocytic, acute; hematologic malignancy; dna; heterozygosity; tumor suppressor proteins; daunorubicin; promyelocytic leukemia; fibroblasts; chromosome translocation; dna sequence; dna mutational analysis; gene dosage; retinoic acid; dna determination; genes, tumor suppressor; growth inhibition; tretinoin; single strand conformation polymorphism; polymorphism, single-stranded conformational; pml gene; humans; prognosis; human; priority journal; article
Journal Title: Blood
Volume: 103
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2004-03-15
Start Page: 2358
End Page: 2362
Language: English
DOI: 10.1182/blood-2003-07-2200
PROVIDER: scopus
PUBMED: 14630830
DOI/URL:
Notes: Blood -- Cited By (since 1996):43 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus
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MSK Authors
  1. Khedoudja Nafa
    184 Nafa
  2. Taha Merghoub
    209 Merghoub
  3. Stephen D Nimer
    345 Nimer