Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL

Romain Guièze; Pauline Robbe; Ruth Clifford; Sophie De Guibert; Bruno Pereira; Adele Timbs; Marie Sarah Dilhuydy; Maite Cabes; Loïc Ysebaert; Adam Burns; Florence Nguyen-Khac; Frédéric Davi; Lauren Véronèse; Patricia Combes; Magali Le Garff-Tavernier; Véronique Leblond; Hélène Merle-Béral; Reem Alsolami; Angela Hamblin; Joanne Mason; Andrew Pettitt; Peter Hillmen; Jenny Taylor; Samantha J.L. Knight; Olivier Tournilhac; Anna Schuh

doi:10.1182/blood-2015-05-647578

Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL

Romain Guièze, Pauline Robbe, Ruth Clifford, Sophie De Guibert, Bruno Pereira, Adele Timbs, Marie Sarah Dilhuydy, Maite Cabes, Loïc Ysebaert, Adam Burns, Florence Nguyen-Khac, Frédéric Davi, Lauren Véronèse, Patricia Combes, Magali Le Garff-Tavernier, Véronique Leblond, Hélène Merle-Béral, Reem Alsolami, Angela Hamblin, Joanne MasonAndrew Pettitt, Peter Hillmen, Jenny Taylor, Samantha J.L. Knight, Olivier Tournilhac, Anna Schuh

Research output: Contribution to journal › Article › peer-review

Abstract

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 andcombinations of recurrentgene mutations. Thenumberof 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 multiplehit profilewasassociated with a medianprogression-free survival of 12monthscompared 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.

Original language	English
Article number	647578
Pages (from-to)	2110-2117
Number of pages	8
Journal	Blood
Volume	126
Issue number	18
DOIs	https://doi.org/10.1182/blood-2015-05-647578
Publication status	Published - 29 Oct 2015
Externally published	Yes

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Guièze, R., Robbe, P., Clifford, R., De Guibert, S., Pereira, B., Timbs, A., Dilhuydy, M. S., Cabes, M., Ysebaert, L., Burns, A., Nguyen-Khac, F., Davi, F., Véronèse, L., Combes, P., Garff-Tavernier, M. L., Leblond, V., Merle-Béral, H., Alsolami, R., Hamblin, A., ... Schuh, A. (2015). Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. Blood, 126(18), 2110-2117. Article 647578. https://doi.org/10.1182/blood-2015-05-647578

@article{0795ec355cbb4fdab7616f85bf55fefc,

title = "Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL",

abstract = "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 andcombinations of recurrentgene mutations. Thenumberof 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 multiplehit profilewasassociated with a medianprogression-free survival of 12monthscompared 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.",

author = "Romain Gui{\`e}ze and Pauline Robbe and Ruth Clifford and {De Guibert}, Sophie and Bruno Pereira and Adele Timbs and Dilhuydy, {Marie Sarah} and Maite Cabes and Lo{\"i}c Ysebaert and Adam Burns and Florence Nguyen-Khac and Fr{\'e}d{\'e}ric Davi and Lauren V{\'e}ron{\`e}se and Patricia Combes and Garff-Tavernier, {Magali Le} and V{\'e}ronique Leblond and H{\'e}l{\`e}ne Merle-B{\'e}ral and Reem Alsolami and Angela Hamblin and Joanne Mason and Andrew Pettitt and Peter Hillmen and Jenny Taylor and Knight, {Samantha J.L.} and Olivier Tournilhac and Anna Schuh",

note = "Publisher Copyright: {\textcopyright} 2015 by The American Society of Hematology.",

year = "2015",

month = oct,

day = "29",

doi = "10.1182/blood-2015-05-647578",

language = "English",

volume = "126",

pages = "2110--2117",

journal = "Blood",

issn = "0006-4971",

number = "18",

}

Guièze, R, Robbe, P, Clifford, R, De Guibert, S, Pereira, B, Timbs, A, Dilhuydy, MS, Cabes, M, Ysebaert, L, Burns, A, Nguyen-Khac, F, Davi, F, Véronèse, L, Combes, P, Garff-Tavernier, ML, Leblond, V, Merle-Béral, H, Alsolami, R, Hamblin, A, Mason, J, Pettitt, A, Hillmen, P, Taylor, J, Knight, SJL, Tournilhac, O & Schuh, A 2015, 'Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL', Blood, vol. 126, no. 18, 647578, pp. 2110-2117. https://doi.org/10.1182/blood-2015-05-647578

TY - JOUR

T1 - Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL

AU - Guièze, Romain

AU - Robbe, Pauline

AU - Clifford, Ruth

AU - De Guibert, Sophie

AU - Pereira, Bruno

AU - Timbs, Adele

AU - Dilhuydy, Marie Sarah

AU - Cabes, Maite

AU - Ysebaert, Loïc

AU - Burns, Adam

AU - Nguyen-Khac, Florence

AU - Davi, Frédéric

AU - Véronèse, Lauren

AU - Combes, Patricia

AU - Garff-Tavernier, Magali Le

AU - Leblond, Véronique

AU - Merle-Béral, Hélène

AU - Alsolami, Reem

AU - Hamblin, Angela

AU - Mason, Joanne

AU - Pettitt, Andrew

AU - Hillmen, Peter

AU - Taylor, Jenny

AU - Knight, Samantha J.L.

AU - Tournilhac, Olivier

AU - Schuh, Anna

PY - 2015/10/29

Y1 - 2015/10/29

N2 - 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 andcombinations of recurrentgene mutations. Thenumberof 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 multiplehit profilewasassociated with a medianprogression-free survival of 12monthscompared 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.

AB - 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 andcombinations of recurrentgene mutations. Thenumberof 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 multiplehit profilewasassociated with a medianprogression-free survival of 12monthscompared 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.

UR - http://www.scopus.com/inward/record.url?scp=84945961824&partnerID=8YFLogxK

U2 - 10.1182/blood-2015-05-647578

DO - 10.1182/blood-2015-05-647578

M3 - Article

C2 - 26316624

AN - SCOPUS:84945961824

SN - 0006-4971

VL - 126

SP - 2110

EP - 2117

JO - Blood

JF - Blood

IS - 18

M1 - 647578

ER -

Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL

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