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Genetic analysis of dasatinib-treated chronic myeloid leukemia rapidly developing into acute myeloid leukemia with monosomy 7 in Philadelphia-negative cells.

Larsson, Nina LU ; Billström, Rolf; Lilljebjörn, Henrik LU ; Lassen, Carin LU ; Richter, Johan LU ; Ekblom, Marja LU and Fioretos, Thoas LU (2010) In Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00 199(2). p.89-95
Abstract
Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Consequently, there is a need to characterize the clinical features of such cases and to increase our understanding of the pathogenetic mechanisms underlying the emergence of clonal cytogenetic changes in Ph(-) cells. To date, most cases reported have received treatment with imatinib. Here we describe the case of a patient with CML... (More)
Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Consequently, there is a need to characterize the clinical features of such cases and to increase our understanding of the pathogenetic mechanisms underlying the emergence of clonal cytogenetic changes in Ph(-) cells. To date, most cases reported have received treatment with imatinib. Here we describe the case of a patient with CML who developed monosomy 7 in Ph(-) cells during dasatinib therapy. At 20 months after dasatinib initiation, the patient developed MDS, which rapidly progressed into AML. Genome-wide 500K SNP array analysis of the monosomy 7 clone revealed no acquired submicroscopic copy number changes. Given the strong association between monosomy 7 and mutation of genes involved in the RAS pathway in juvenile myelomonocytic leukemia, we also screened for pathogenetic variants in KRAS, NRAS, and PTPN11, but did not detect any changes. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00
volume
199
issue
2
pages
89 - 95
publisher
Elsevier
external identifiers
  • wos:000278156100004
  • pmid:20471511
  • scopus:77952772669
ISSN
0165-4608
DOI
10.1016/j.cancergencyto.2010.02.005
language
English
LU publication?
yes
id
d628734a-a83a-4cf9-bbb0-dc1683bf51c8 (old id 1610215)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20471511?dopt=Abstract
date added to LUP
2010-06-02 10:42:34
date last changed
2017-01-01 07:52:12
@article{d628734a-a83a-4cf9-bbb0-dc1683bf51c8,
  abstract     = {Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Consequently, there is a need to characterize the clinical features of such cases and to increase our understanding of the pathogenetic mechanisms underlying the emergence of clonal cytogenetic changes in Ph(-) cells. To date, most cases reported have received treatment with imatinib. Here we describe the case of a patient with CML who developed monosomy 7 in Ph(-) cells during dasatinib therapy. At 20 months after dasatinib initiation, the patient developed MDS, which rapidly progressed into AML. Genome-wide 500K SNP array analysis of the monosomy 7 clone revealed no acquired submicroscopic copy number changes. Given the strong association between monosomy 7 and mutation of genes involved in the RAS pathway in juvenile myelomonocytic leukemia, we also screened for pathogenetic variants in KRAS, NRAS, and PTPN11, but did not detect any changes.},
  author       = {Larsson, Nina and Billström, Rolf and Lilljebjörn, Henrik and Lassen, Carin and Richter, Johan and Ekblom, Marja and Fioretos, Thoas},
  issn         = {0165-4608},
  language     = {eng},
  number       = {2},
  pages        = {89--95},
  publisher    = {Elsevier},
  series       = {Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00},
  title        = {Genetic analysis of dasatinib-treated chronic myeloid leukemia rapidly developing into acute myeloid leukemia with monosomy 7 in Philadelphia-negative cells.},
  url          = {http://dx.doi.org/10.1016/j.cancergencyto.2010.02.005},
  volume       = {199},
  year         = {2010},
}