SF3B1 and IGHV gene mutation status predict poor prognosis in Japanese CLL patients

Int J Hematol. 2016 Feb;103(2):219-26. doi: 10.1007/s12185-015-1912-z. Epub 2015 Nov 20.

Abstract

The incidence of chronic lymphocytic leukemia (CLL) is low in Japan. The clinical course ranges from very indolent to rapidly progressive. Recently, several reports have indicated that mutation of the splicing factor 3b, subunit 1 (SF3B1) gene in CLL is predictive of a poor prognosis. Here, we investigated the SF3B1 mutational status of Japanese CLL patients and clarified the association between SF3B1 mutational status and prognostic factors. One hundred and two patients that were referred to our institutions between 1999 and 2013 were enrolled. Mutation analysis of SF3B1 (n = 87) and of the immunoglobulin heavy chain gene (IGHV) (n = 102) was performed at diagnosis. FISH analysis of del(11)(q22) was performed for 17 patients. Seven patients have SF3B1 mutation (8.0 %: K700E, 5/7; G742D, 1/7 and Y623C, 1/7). The median survival times for patients with mutated and non-mutated SF3B1 were 53 and 130 months, respectively. Overall survival of the mutated SF3B1 group was significantly lower than that of the non-mutated group (p = 0.0187). No relationship was observed between IGHV mutational status and SF3B1 mutation. There was no patient with SF3B1 mutation in the IGHV1-69 population (0/2). In conclusion, mutation of SF3B1 at diagnosis in Japanese CLL patients is predictive of a poor prognosis.

Keywords: Chronic lymphocytic leukemia; IGHV mutational status; SF3B1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Phosphoproteins / genetics*
  • Predictive Value of Tests
  • Prognosis
  • RNA Splicing Factors / genetics*

Substances

  • Immunoglobulin Heavy Chains
  • Phosphoproteins
  • RNA Splicing Factors
  • SF3B1 protein, human