期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 176, 期 1, 页码 86-91出版社
WILEY-BLACKWELL
DOI: 10.1111/bjh.14413
关键词
primary chemoresistance; paediatric leukaemia; cytogenetically normal acute myeloid leukaemia; targeted deep sequencing genomics; induction failure
类别
资金
- NIH [R21 CA188881, K08 CA160660, P30 CA008748, U10 CA180899]
- Burroughs Wellcome Fund
- Alex's Lemonade Stand Foundation
- Gabrielle's Angel Foundation
- Josie Robertson Investigator Program
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.
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