FBXW7 mutation in adult T-cell and B-cell acute lymphocytic leukemias

Jee Hoon Song, Nikolai Schnittke, April Zaat, Christine S. Walsh, Carl W. Miller

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The FBXW7 (also known as AGO, hCDC4, FBW7 and SEL-10) gene encodes a subunit of an ubiquitin protein ligase which regulates levels of cyclin E, NOTCH and other proteins. Engineered FBXW7 null cells display cell cycle and chromosome stability defects. Mutations of FBXW7 have been found in human colorectal, ovarian, endometrial tumors and T-cell acute lymphocytic leukemias. Prompted by these findings we have examined acute myeloid leukemia, non-Hodgkin's lymphoma, T-cell acute lymphocytic leukemia, B-cell acute lymphocytic leukemia and adult T-cell leukemia DNA for mutations of the FBXW7 gene. Mutations were detected by PCR-SSCP of all coding exons of the three isoforms of FBXW7, shifted bands were direct sequenced. As expected, mutations were found in T-cell acute lymphocytic leukemias. However mutations of FBXW7 were also found in four of 118 B-cell acute lymphocytic leukemias and one of 24 adult T-cell leukemia samples. The nucleotide changes consisted of an insertion, resulting in a frameshift mutation, and missense mutations of highly conserved residues. All mutations affected the FBXW7 target interacting domain. These observations suggest that disruption of FBXW7 has a role in several forms of lymphocytic leukemias and not exclusively T-cell acute lymphocytic leukemia.

Original languageEnglish (US)
Pages (from-to)1751-1755
Number of pages5
JournalLeukemia Research
Volume32
Issue number11
DOIs
StatePublished - Nov 2008
Externally publishedYes

Keywords

  • FBXW7
  • Lymphocytic leukemia
  • Mutation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'FBXW7 mutation in adult T-cell and B-cell acute lymphocytic leukemias'. Together they form a unique fingerprint.

Cite this