Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia

Carmela Gurrieri, Khedoudja Nafa, Taha Merghoub, Rosa Bernardi, Paola Capodieci, Andrea Biondi, Stephen D Nimer, Dan Douer, Carlos Cordon-Cardo, Robert Gallagher, Pier Paolo Pandolfi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2358-2362
Number of pages5
JournalBlood
Volume103
Issue number6
DOIs
StatePublished - Mar 15 2004
Externally publishedYes

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Acute Promyelocytic Leukemia
Tretinoin
Tumor Suppressor Genes
Tumors
Leukemia
Genes
Mutation
Acid resistance
DNA sequences
Polymorphism
Alleles
Genetic Translocation
DNA
Neoplasms
Proteins
Phenotype
Growth

ASJC Scopus subject areas

  • Hematology

Cite this

Gurrieri, C., Nafa, K., Merghoub, T., Bernardi, R., Capodieci, P., Biondi, A., ... Pandolfi, P. P. (2004). Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. Blood, 103(6), 2358-2362. https://doi.org/10.1182/blood-2003-07-2200

Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. / Gurrieri, Carmela; Nafa, Khedoudja; Merghoub, Taha; Bernardi, Rosa; Capodieci, Paola; Biondi, Andrea; Nimer, Stephen D; Douer, Dan; Cordon-Cardo, Carlos; Gallagher, Robert; Pandolfi, Pier Paolo.

In: Blood, Vol. 103, No. 6, 15.03.2004, p. 2358-2362.

Research output: Contribution to journalArticle

Gurrieri, C, Nafa, K, Merghoub, T, Bernardi, R, Capodieci, P, Biondi, A, Nimer, SD, Douer, D, Cordon-Cardo, C, Gallagher, R & Pandolfi, PP 2004, 'Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia', Blood, vol. 103, no. 6, pp. 2358-2362. https://doi.org/10.1182/blood-2003-07-2200
Gurrieri C, Nafa K, Merghoub T, Bernardi R, Capodieci P, Biondi A et al. Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. Blood. 2004 Mar 15;103(6):2358-2362. https://doi.org/10.1182/blood-2003-07-2200
Gurrieri, Carmela ; Nafa, Khedoudja ; Merghoub, Taha ; Bernardi, Rosa ; Capodieci, Paola ; Biondi, Andrea ; Nimer, Stephen D ; Douer, Dan ; Cordon-Cardo, Carlos ; Gallagher, Robert ; Pandolfi, Pier Paolo. / Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. In: Blood. 2004 ; Vol. 103, No. 6. pp. 2358-2362.
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