title: Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  Mutations in the PHF6 gene were recently described in patients with T-cell acute lymphoblastic leukemia and in those with acute myeloid leukemia. The present study was designed to determine the prevalence of PHF6 gene alterations in T-cell acute lymphoblastic leukemia.
  
  
  METHODS
  We analyzed the incidence and prognostic value of PHF6 mutations in 96 Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were screened by real-time quantitative polymerase chain reaction and array-based comparative genomic hybridization. Patients were also investigated for NOTCH1, FBXW7, WT1, and JAK1 mutations together with CALM-AF10, SET-NUP214, and SIL-TAL1 gene rearrangements.
  
  
  RESULTS
  PHF6 mutations were identified in 11/59 (18.6%) adult and 2/37 (5.4%) pediatric cases of T-cell acute lymphoblastic leukemia, these incidences being significantly lower than those recently reported. Although PHF6 is X-linked and mutations have been reported to occur almost exclusively in male patients, we found no sex difference in the incidences of PHF6 mutations in Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were detected in 2/79 (2.5%) patients analyzed. NOTCH1 mutations, FBXW7 mutations, WT1 mutations, JAK1 mutations, SIL-TAL1 fusions, SET-NUP214 fusions and CALM-AF10 fusions were present in 44/96 (45.8%), 9/96 (9.4%), 4/96 (4.1%), 3/49 (6.1%), 9/48 (18.8%), 3/48 (6.3%) and 0/48 (0%) of patients, respectively. The molecular genetic markers most frequently associated with PHF6 mutations were NOTCH1 mutations (P=0.003), SET-NUP214 rearrangements (P=0.002), and JAK1 mutations (P=0.005). No differences in disease-free survival and overall survival between T-cell acute lymphoblastic leukemia patients with and without PHF6 mutations were observed in a short-term follow-up.
  
  
  CONCLUSIONS
  Overall, these results indicate that, in T-cell acute lymphoblastic leukemia, PHF6 mutations are a recurrent genetic abnormality associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214.
authors: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu province, People's Republic of China.
authors: Qian
authors: Q
authors: Wang
authors: Huiying
authors: H
authors: Qiu
authors: Hui
authors: H
authors: Jiang
authors: Lili
authors: L
authors: Wu
authors: Shasha
authors: S
authors: Dong
authors: Jinlan
authors: J
authors: Pan
authors: Wenjuan
authors: W
authors: Wang
authors: Nana
authors: N
authors: Ping
authors: Jing
authors: J
authors: Xia
authors: Aining
authors: A
authors: Sun
authors: Depei
authors: D
authors: Wu
authors: Yongquan
authors: Y
authors: Xue
authors: Hans G
authors: HG
authors: Drexler
authors: Roderick A F
authors: RA
authors: Macleod
authors: Suning
authors: S
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins; D005260:Female; D005819:Genetic Markers; D056488:Histone Chaperones / Q000235:genetics*; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D051881:Receptor, Notch1 / Q000235:genetics*; D012097:Repressor Proteins; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D056488:Histone Chaperones; C497761:NOTCH1 protein, human; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C502542:PHF6 protein, human; D051881:Receptor, Notch1; D012097:Repressor Proteins; C513473:SET protein, human; D014157:Transcription Factors; C507904:JAK1 protein, human; D053613:Janus Kinase 1