PHF6 Mutations in T-cell Acute Lymphoblastic Leukemia

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Mar 16

PMID 20228800

Citations 160

Authors

Pieter Van Vlierberghe

Teresa Palomero

Hossein Khiabanian

Joni Van der Meulen

Mireia Castillo

Nadine Van Roy

Barbara De Moerloose

Jan Philippe

Sara Gonzalez-Garcia

Maria L Toribio

Tom Taghon

Linda Zuurbier

Barbara Cauwelier

Christine J Harrison

Claire Schwab

Markus Pisecker

Sabine Strehl

Anton W Langerak

Jozef Gecz

Edwin Sonneveld

Rob 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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Loss of PHF6 causes spontaneous seizures, enlarged brain ventricles and altered transcription in the cortex of a mouse model of the Börjeson-Forssman-Lehmann intellectual disability syndrome.

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