title: Co-existence ofPHF6andNOTCH1mutations in adult T-cell acute lymphoblastic leukemia.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) results from the collaboration of multiple genetic abnormalities in the transformation of T-cell progenitors. Plant homeodomain finger protein 6 (PHF6) has recently been established as a key tumor suppressor, which is mutated in T-ALL; however, the clinical significance ofPHF6mutations has not been fully determined in adult T-ALL. In the present study, amplification of thePHF6exons was performed, followed by DNA sequencing to identify the genomic mutations and examine the expression ofPHF6in adult patients with T-ALL. The correlation betweenPHF6mutations and clinical features was also analyzed using a χ2test, and betweenPHF6mutations and survival curve using the Kaplan-Meier methods.PHF6mutations were detected in 27.1% of the Chinese adults with T-ALL (16/59), 10 of which were found to be novel mutations. A significantly lower expression level ofPHF6was observed in T-ALL patients with PHF6 mutations compared with those without mutations. Of the observed mutations in PHF6, 6/16 were frame-shift mutations, indicating aPHF6dysfunction in those patients. Of note,PHF6mutations were found to be significantly associated with older age, lower hemoglobin levels, higher frequency of CD13 positivity and higher incidence of splenomegaly or lymphadenopathy. Furthermore,PHF6mutations were found to be significantly correlated with Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) mutations. The patients with T-ALL with co-existence of the two mutations had a significantly shorter event-free survival and a poor prognosis. The present results indicated thatPHF6is inactivated in adult T-ALL, due to its low expression and mutations. The present data indicated the synergistic effect ofPHF6andNOTCH1mutations, as well as their co-existence, on the oncogenesis of adult T-ALL, and their potential as a prognostic marker for the disease.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Lichan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Nanjing, Nanjing, Jiangsu 320100, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Biology, University of Wisconsin-Stout, Menomonie, WI 54751, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Olson
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China; Department of Hematology, Zhongda Hospital, Southeast University Medical School, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ge
keywords: Notch homolog 1; Plant homeodomain finger protein 6; T-cell acute lymphoblastic leukemia; mutations; translocation-associated (Drosophila)