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“Double‐hit” chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain
Author(s) -
Chapiro Elise,
Lesty Claude,
Gabillaud Clémentine,
Durot Eric,
Bouzy Simon,
Armand Marine,
Le GarffTavernier Magali,
Bougacha Nadia,
Struski Stéphanie,
Bidet Audrey,
Laharanne Elodie,
Barin Carole,
Veronese Lauren,
Prié Nolwen,
Eclache Virginie,
Gaillard Baptiste,
Michaux Lucienne,
Lefebvre Christine,
Gaillard JeanBaptiste,
Terré Christine,
Penther Dominique,
Bastard Christian,
Nadal Nathalie,
FertFerrer Sandra,
Auger Nathalie,
Godon Catherine,
Sutton Laurent,
Tournilhac Olivier,
Susin Santos A.,
NguyenKhac Florence
Publication year - 2018
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24990
Subject(s) - isochromosome , chromosomal translocation , medicine , chronic lymphocytic leukemia , monosomy , biology , karyotype , oncology , chromosome abnormality , cytogenetics , univariate analysis , chromosome , leukemia , genetics , multivariate analysis , gene
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p‐) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p‐ and the additional aberrations influenced the prognosis in a series of 195 patients with 17p‐CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment‐free survival, and i(17q) ( P = .04), unbalanced translocations ( P = .03) and 8q24 gain ( P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this “double‐hit” CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p‐ CLL.