PMID- 28602946
OWN - NLM
STAT- MEDLINE
DCOM- 20170929
LR  - 20180224
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 53
DP  - 2017 Sep
TI  - Whole-genome analysis reveals unexpected dynamics of mutant subclone development 
      in a patient with JAK2-V617F-positive chronic myeloid leukemia.
PG  - 48-58
LID - S0301-472X(17)30192-3 [pii]
LID - 10.1016/j.exphem.2017.05.007 [doi]
AB  - We report here the first use of whole-genome sequencing (WGS) to examine the 
      initial clonal dynamics in an unusual patient with chronic myeloid leukemia 
      (CML), who presented in chronic phase (CP) with doubly marked 
      BCR-ABL1(+)/JAK2(V617F)-mutant cells and, over a 9-year period, progressed into 
      an accelerated phase (AP) and then terminal blast phase (BP). WGS revealed that 
      the diagnostic cells also contained mutations in ASXL1, SEC23B, MAD1L1, and RREB1 
      as well as 12,000 additional uncommon DNA variants. WGS of endothelial cells 
      generated from circulating precursors revealed many of these were shared with the 
      CML clone. Surprisingly, WGS of induced pluripotent stem cells (iPSCs) derived 
      from the AP cells revealed only six additional coding somatic mutations, despite 
      retention by the hematopoietic progeny of the parental AP cell levels of BCR-ABL1 
      expression and sensitivity to imatinib and pimozide. Limited analysis of BP cells 
      revealed independent subclonal progression to homozygosity of the MAD1L1 and 
      RREB1 variants. MAD1L1 and SEC23B mutations were also identified in 2 of 101 
      cases of myeloproliferative neoplasms, but not in 42 healthy subjects. These 
      findings challenge historic concepts of clonal evolution in CML.
CI  - Copyright (c) 2017 ISEH - International Society for Experimental Hematology. All 
      rights reserved.
FAU - Sloma, Ivan
AU  - Sloma I
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Service d'Hematologie Biologique, Institut Federatif 
      d'Hematologie Interpole Paris Sud-IFHIPS (AP-HP) Kremlin Bicetre, Paris, France; 
      Universite Paris-Sud, Faculte de Medecine Kremlin Bicetre, and INSERM UMS 33, 
      Villejuif, France.
FAU - Mitjavila-Garcia, Maria Teresa
AU  - Mitjavila-Garcia MT
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France.
FAU - Feraud, Olivier
AU  - Feraud O
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France.
FAU - Griscelli, Frank
AU  - Griscelli F
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France; Universite Paris Descartes, Sorbonne Paris Cite, 
      Faculte des Sciences Pharmaceutiques et Biologiques, Paris, France.
FAU - Oudrhiri, Noufissa
AU  - Oudrhiri N
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France.
FAU - El Marsafy, Sanaa
AU  - El Marsafy S
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France.
FAU - Gobbo, Emilie
AU  - Gobbo E
AD  - Human Pluripotent Stem Cell Core Facility, ESTeam Paris Sud-INGESTEM, Villejuif, 
      France.
FAU - Divers, Dominique
AU  - Divers D
AD  - Human Pluripotent Stem Cell Core Facility, ESTeam Paris Sud-INGESTEM, Villejuif, 
      France.
FAU - Proust, Alexis
AU  - Proust A
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France.
FAU - Smadja, David M
AU  - Smadja DM
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Faculte des Sciences 
      Pharmaceutiques et Biologiques, Paris, France; AP-HP, Hopital Europeen Georges 
      Pompidou, Service d'Hematologie Biologique, Paris, France.
FAU - Desterke, Christophe
AU  - Desterke C
AD  - Universite Paris-Sud, Faculte de Medecine Kremlin Bicetre, and INSERM UMS 33, 
      Villejuif, France.
FAU - Carles, Annaick
AU  - Carles A
AD  - University of British Columbia, Centre for High-Throughput Biology and Department 
      of Microbiology & Immunology, Vancouver, BC, Canada.
FAU - Ma, Yusanna
AU  - Ma Y
AD  - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, 
      Canada.
FAU - Hirst, Martin
AU  - Hirst M
AD  - University of British Columbia, Centre for High-Throughput Biology and Department 
      of Microbiology & Immunology, Vancouver, BC, Canada; Canada's Michael Smith 
      Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
FAU - Marra, Marco A
AU  - Marra MA
AD  - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, 
      Canada; Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.
FAU - Eaves, Connie J
AU  - Eaves CJ
AD  - Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada; Department of 
      Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
FAU - Bennaceur-Griscelli, Annelise
AU  - Bennaceur-Griscelli A
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Service d'Hematologie Biologique, Institut Federatif 
      d'Hematologie Interpole Paris Sud-IFHIPS (AP-HP) Kremlin Bicetre, Paris, France; 
      Universite Paris-Sud, Faculte de Medecine Kremlin Bicetre, and INSERM UMS 33, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France.
FAU - Turhan, Ali G
AU  - Turhan AG
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U935, 
      Villejuif, France; Service d'Hematologie Biologique, Institut Federatif 
      d'Hematologie Interpole Paris Sud-IFHIPS (AP-HP) Kremlin Bicetre, Paris, France; 
      Universite Paris-Sud, Faculte de Medecine Kremlin Bicetre, and INSERM UMS 33, 
      Villejuif, France; Human Pluripotent Stem Cell Core Facility, ESTeam Paris 
      Sud-INGESTEM, Villejuif, France. Electronic address: turviv33@gmail.com.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170608
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MAD1L1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RREB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Cell Cycle Proteins/genetics
MH  - DNA-Binding Proteins/genetics
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Induced Pluripotent Stem Cells/physiology
MH  - Janus Kinase 2/*genetics
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Nuclear Proteins/genetics
MH  - Transcription Factors/genetics
EDAT- 2017/06/13 06:00
MHDA- 2017/09/30 06:00
CRDT- 2017/06/13 06:00
PHST- 2017/05/01 00:00 [received]
PHST- 2017/05/20 00:00 [revised]
PHST- 2017/05/22 00:00 [accepted]
PHST- 2017/06/13 06:00 [pubmed]
PHST- 2017/09/30 06:00 [medline]
PHST- 2017/06/13 06:00 [entrez]
AID - S0301-472X(17)30192-3 [pii]
AID - 10.1016/j.exphem.2017.05.007 [doi]
PST - ppublish
SO  - Exp Hematol. 2017 Sep;53:48-58. doi: 10.1016/j.exphem.2017.05.007. Epub 2017 Jun 
      8.