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

doi:10.1111/bjh.14413

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

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

28 Scopus citations

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 language	English
Pages (from-to)	86-91
Number of pages	6
Journal	British Journal of Haematology
Volume	176
Issue number	1
DOIs	https://doi.org/10.1111/bjh.14413
State	Published - 1 Jan 2017
Externally published	Yes

Keywords

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

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10.1111/bjh.14413

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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

@article{e90362aac870402a9f9b54fcedc060a0,

title = "Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia",

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.",

keywords = "cytogenetically normal acute myeloid leukaemia, induction failure, paediatric leukaemia, primary chemoresistance, targeted deep sequencing genomics",

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

note = "Publisher Copyright: {\textcopyright} 2016 John Wiley \& Sons Ltd",

year = "2017",

month = jan,

day = "1",

doi = "10.1111/bjh.14413",

language = "English",

volume = "176",

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Brown, FC, Cifani, P, Drill, E, He, J, Still, E, Zhong, S, Balasubramanian, S, Pavlick, D, Yilmazel, B, Knapp, KM, Alonzo, TA, Meshinchi, S, Stone, RM, Kornblau, SM, Marcucci, G, Gamis, AS, Byrd, JC, Gonen, M, Levine, RL & Kentsis, A 2017, 'Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia', British Journal of Haematology, vol. 176, no. 1, pp. 86-91. https://doi.org/10.1111/bjh.14413

TY - JOUR

T1 - Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia

AU - Brown, Fiona C.

AU - Cifani, Paolo

AU - Drill, Esther

AU - He, Jie

AU - Still, Eric

AU - Zhong, Shan

AU - Balasubramanian, Sohail

AU - Pavlick, Dean

AU - Yilmazel, Bahar

AU - Knapp, Kristina M.

AU - Alonzo, Todd A.

AU - Meshinchi, Soheil

AU - Stone, Richard M.

AU - Kornblau, Steven M.

AU - Marcucci, Guido

AU - Gamis, Alan S.

AU - Byrd, John C.

AU - Gonen, Mithat

AU - Levine, Ross L.

AU - Kentsis, Alex

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - cytogenetically normal acute myeloid leukaemia

KW - induction failure

KW - paediatric leukaemia

KW - primary chemoresistance

KW - targeted deep sequencing genomics

UR - https://www.scopus.com/pages/publications/84995469181

U2 - 10.1111/bjh.14413

DO - 10.1111/bjh.14413

M3 - Article

C2 - 27766616

AN - SCOPUS:84995469181

SN - 0007-1048

VL - 176

SP - 86

EP - 91

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 1

ER -

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

Abstract

Keywords

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