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Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia

Hyrenius-Wittsten, Axel LU ; Sturesson, Helena LU ; Bidgoli, Mahtab LU ; Jonson, Tord LU ; Ehinger, Mats LU ; Lilljebjörn, Henrik LU orcid ; Scheding, Stefan LU and Andersson, Anna K. LU orcid (2016) In Genes Chromosomes and Cancer 55(11). p.847-854
Abstract

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number... (More)

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non-silent somatic mutations, including DNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN-U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, for example, the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes Chromosomes and Cancer
volume
55
issue
11
pages
8 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:84986597335
  • pmid:27240832
  • wos:000383584300003
ISSN
1045-2257
DOI
10.1002/gcc.22384
language
English
LU publication?
yes
id
bfbb4c7f-191b-4429-9e00-783d4709bb21
date added to LUP
2016-10-03 12:39:48
date last changed
2025-01-12 12:26:33
@article{bfbb4c7f-191b-4429-9e00-783d4709bb21,
  abstract     = {{<p>Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non-silent somatic mutations, including DNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN-U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, for example, the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs.</p>}},
  author       = {{Hyrenius-Wittsten, Axel and Sturesson, Helena and Bidgoli, Mahtab and Jonson, Tord and Ehinger, Mats and Lilljebjörn, Henrik and Scheding, Stefan and Andersson, Anna K.}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{847--854}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes Chromosomes and Cancer}},
  title        = {{Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia}},
  url          = {{https://lup.lub.lu.se/search/files/22339043/13429645.pdf}},
  doi          = {{10.1002/gcc.22384}},
  volume       = {{55}},
  year         = {{2016}},
}