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. 2011 Jan;25(1):130-4.
doi: 10.1038/leu.2010.247. Epub 2010 Oct 29.

PHF6 mutations in adult acute myeloid leukemia

P Van Vlierberghe  1 , J Patel, O Abdel-Wahab, C Lobry, C V Hedvat, M Balbin, C Nicolas, A R Payer, H F Fernandez, M S Tallman, E Paietta, A Melnick, P Vandenberghe, F Speleman, I Aifantis, J Cools, R Levine, A Ferrando
Affiliations

PHF6 mutations in adult acute myeloid leukemia

P Van Vlierberghe et al. Leukemia. 2011 Jan.

Abstract

Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic lesions in PHF6 found in AMLs are frameshift and nonsense mutations distributed through the gene or point mutations involving the second plant homeodomain (PHD)-like domain of the protein. As in the case of T-ALL, where PHF6 alterations are found almost exclusively in males, mutations in PHF6 were seven times more prevalent in males than in females with AML. Overall, these results identify PHF6 as a tumor suppressor gene mutated in AML and extend the role of this X-linked tumor suppressor gene in the pathogenesis of hematologic tumors.

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Conflict of interest statement

Disclosure of conflicts of interest

No conflicts of interest to disclose.

Figures

Figure 1
Figure 1. PHF6 mutations in AML
(A) Schematic representation of the PHF6 protein depicting the location of 4 nuclear localization signals and 2 imperfect PHD zinc finger domains. Overview of PHF6 mutations identified in primary AML samples. Filled circles represent nonsense and frameshift mutations, whereas missense mutations are depicted as open circles. The circle filled in gray indicates a frameshift PHF6 mutation identified in a female AML sample. (B) Representative DNA sequencing chromatograms of AML DNA samples showing mutations in exons 7, 9 and 10 of PHF6.
Figure 2
Figure 2. Phf6 expression in HSC and myeloid progenitor populations
Quantitative RT-PCR analysis of murine Phf6 expression normalized to Gapdh in HSC, myeloid progenitor and lymphoid populations. Error bars indicate s.d.
Figure 3
Figure 3. Gender distribution of PHF6 mutations in AML
Differential distribution of PHF6 mutations in AML samples from male and female patients.
See this image and copyright information in PMC

References

    1. Renneville A, Roumier C, Biggio V, Nibourel O, Boissel N, Fenaux P, et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia. 2008 May;22(5):915–931. - PubMed
    1. Dohner K, Dohner H. Molecular characterization of acute myeloid leukemia. Haematologica. 2008 Jul;93(7):976–982. - PubMed
    1. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009 Jul;41(7):838–842. - PubMed
    1. Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009 Jun 18;113(25):6403–6410. - PMC - PubMed
    1. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009 May 28;360(22):2289–2301. - PubMed

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