Advanced

Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate.

Barbouti, Aikaterini; Ahlgren, Tomas; Johansson, Bertil LU ; Höglund, Mattias LU ; Lassen, Carin LU ; Turesson, Ingemar LU ; Mitelman, Felix LU and Fioretos, Thoas LU (2003) In British Journal of Haematology 122(1). p.85-93
Abstract
Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable... (More)
Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable improvements in the clinical and laboratory features were noted, and the frequency of ABL1-rearranged peripheral blood cells decreased from 56% to 11%. At d 92, an additional t(12;13)(p12;q13), with the 12p breakpoint proximal to ETV6, was found. The patient relapsed into BC 126 d after the start of the imatinib mesylate treatment and succumbed to the disease shortly afterwards. No mutations in the tyrosine kinase domain of ABL1 of the ETV6/ABL1 fusion were identified in the second BC. However, whereas the ETV6/ABL1 expression was seemingly the same at diagnosis and at second BC, the expression of ETV6 was markedly lower at the second BC. This decreased expression of wild-type ETV6 may have been a contributory factor for the relapse. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Haematology
volume
122
issue
1
pages
85 - 93
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:12823349
  • wos:000183689800010
  • scopus:0038683894
ISSN
0007-1048
DOI
language
English
LU publication?
yes
id
15c4342c-7f2b-4094-9c42-ce0fb0cce7ba (old id 115729)
date added to LUP
2007-07-06 12:45:09
date last changed
2018-05-29 11:58:42
@article{15c4342c-7f2b-4094-9c42-ce0fb0cce7ba,
  abstract     = {Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable improvements in the clinical and laboratory features were noted, and the frequency of ABL1-rearranged peripheral blood cells decreased from 56% to 11%. At d 92, an additional t(12;13)(p12;q13), with the 12p breakpoint proximal to ETV6, was found. The patient relapsed into BC 126 d after the start of the imatinib mesylate treatment and succumbed to the disease shortly afterwards. No mutations in the tyrosine kinase domain of ABL1 of the ETV6/ABL1 fusion were identified in the second BC. However, whereas the ETV6/ABL1 expression was seemingly the same at diagnosis and at second BC, the expression of ETV6 was markedly lower at the second BC. This decreased expression of wild-type ETV6 may have been a contributory factor for the relapse.},
  author       = {Barbouti, Aikaterini and Ahlgren, Tomas and Johansson, Bertil and Höglund, Mattias and Lassen, Carin and Turesson, Ingemar and Mitelman, Felix and Fioretos, Thoas},
  issn         = {0007-1048},
  language     = {eng},
  number       = {1},
  pages        = {85--93},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate.},
  url          = {http://dx.doi.org/},
  volume       = {122},
  year         = {2003},
}