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Details

Autor(en) / Beteiligte
Titel
Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL
Ist Teil von
  • Blood, 2015-10, Vol.126 (18), p.2110-2117
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2015
Quelle
MEDLINE
Beschreibungen/Notizen
  • Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted next-generation sequencing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥2, 1, and 0 in 43 (38%), 49 (43%), and 22 (19%) respectively. Recurrent combinations of ≥2 mutations of TP53, SF3B1, and ATM were found in 22 (19%) patients. This multiple-hit profile was associated with a median progression-free survival of 12 months compared with 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome. •Targeted NGS of relapsed/refractory CLL reveals a high incidence of concurrent mutations that mostly affect the TP53, ATM, and SF3B1 genes.•Concurrent mutations of the TP53, ATM, and/or SF3B1 genes confer short survival in patients with relapsed/refractory CLL.

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