Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia

Fiona C. Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M. Knapp, Todd A. Alonzo, Soheil Meshinchi, Richard M. Stone, Steven M. Kornblau, Guido Marcucci, Alan S. Gamis, John C. Byrd, Mithat Gonen, Ross L. Levine, Alex Kentsis

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Abstract

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.

Original languageEnglish
Pages (from-to)86-91
Number of pages6
JournalBritish Journal of Haematology
Volume176
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

Keywords

  • cytogenetically normal acute myeloid leukaemia
  • induction failure
  • paediatric leukaemia
  • primary chemoresistance
  • targeted deep sequencing genomics

Cite this

Brown, F. C., Cifani, P., Drill, E., He, J., Still, E., Zhong, S., Balasubramanian, S., Pavlick, D., Yilmazel, B., Knapp, K. M., Alonzo, T. A., Meshinchi, S., Stone, R. M., Kornblau, S. M., Marcucci, G., Gamis, A. S., Byrd, J. C., Gonen, M., Levine, R. L., & Kentsis, A. (2017). Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia. British Journal of Haematology, 176(1), 86-91. https://doi.org/10.1111/bjh.14413