PHF6 mutations in T-cell acute lymphoblastic leukemia

Pieter Van Vlierberghe, Teresa Palomero, Hossein Khiabanian, Joni Van Der Meulen, Mireia Castillo, Nadine Van Roy, Barbara De Moerloose, Jan Philippé, Sara González-García, María L. Toribio, Tom Taghon, Linda Zuurbier, Barbara Cauwelier, Christine J. Harrison, Claire Schwab, Markus Pisecker, Sabine Strehl, Anton W. Langerak, Jozef Gecz, Edwin SonneveldRob Pieters, Elisabeth Paietta, Jacob M. Rowe, Peter H. Wiernik, Yves Benoit, Jean Soulier, Bruce Poppe, Xiaopan Yao, Carlos Cordon-Cardo, Jules Meijerink, Raul Rabadan, Frank Speleman, Adolfo Ferrando

Research output: Contribution to journalArticlepeer-review

242 Scopus citations


Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.

Original languageEnglish
Pages (from-to)338-342
Number of pages5
JournalNature Genetics
Issue number4
StatePublished - Apr 2010
Externally publishedYes


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