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TP 53 mutations are associated with mutated MYD 88 and CXCR 4 , and confer an adverse outcome in Waldenström macroglobulinaemia
Author(s) -
Gustine Joshua N.,
Tsakmaklis Nicholas,
Demos Maria G.,
Kofides Amanda,
Chen Jiaji G.,
Liu Xia,
Munshi Manit,
Guerrera Maria L.,
Chan Gloria G.,
Patterson Christopher J.,
Meid Kirsten,
Dubeau Toni,
Yang Guang,
Hunter Zachary R.,
Treon Steven P.,
Castillo Jorge J.,
Xu Lian
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15560
Subject(s) - ibrutinib , sanger sequencing , mutation , medicine , cancer research , genetics , biology , microbiology and biotechnology , gene , leukemia , chronic lymphocytic leukemia
Summary Little is known about TP 53 mutations in Waldenström Macroglobulinaemia ( WM ). We evaluated 265 WM patients for TP 53 mutations by next‐generation sequencing, and validated the findings by Sanger sequencing. TP 53 mutations were identified and validated in 6 (2·6%) patients that impacted the DNA ‐binding domain. All six were MYD 88‐ and CXCR 4 ‐mutated. Ibrutinib showed activity in patients carrying all three mutations. With a median follow‐up of 18 months, 2 (33%) with biallelic TP 53 inactivation died of progressive disease. TP 53 mutations are rare in WM , and associate with MYD 88 and CXCR 4 mutations. WM patients with TP 53 mutations show response to ibrutinib.