liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Clonal conversion of B lymphoid leukemia reveals cross-lineage transfer of malignant states
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Show others and affiliations
2016 (English)In: GENES and DEVELOPMENT, ISSN 0890-9369, Vol. 30, no 22, p. 2486-2499Article in journal (Refereed) Published
Abstract [en]

Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells. Even though the conversion process involved global changes in gene expression and lineage-restricted epigenetic reconfiguration, the malignant phenotype of the cells was preserved, enabling them to expand as T lineage leukemia cells in vivo. Furthermore, while the transformed pro-B cells displayed plasticity toward myeloid lineages, the converted cells failed to cause myeloid leukemia after transplantation. These data provide evidence that a malignant phenotype can be transferred between hematopoietic lineages. This has important implications for modern cancer medicine because lineage targeted treatment of leukemia patients can be predicted to provoke the emergence of phenotypically altered subclones, causing clinical relapse.

Place, publisher, year, edition, pages
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT , 2016. Vol. 30, no 22, p. 2486-2499
Keywords [en]
B-ALL; lineage conversion; transcription factors
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-134094DOI: 10.1101/gad.285536.116ISI: 000390615700003PubMedID: 27913602OAI: oai:DiVA.org:liu-134094DiVA, id: diva2:1067527
Note

Funding Agencies|Swedish Cancer Society; Swedish Childhood Cancer Foundation; Swedish Research Council; Knut and Alice Wallenbergs Foundation; Linkoping University

Available from: 2017-01-22 Created: 2017-01-22 Last updated: 2018-01-13

Open Access in DiVA

fulltext(1878 kB)43 downloads
File information
File name FULLTEXT01.pdfFile size 1878 kBChecksum SHA-512
aa8f55abbc4ea40bc8664fd5f84fb689585097daeec3f27c905cf78834decba07f4b2052f02cd57a7833c931ae18eb5dcb1eb3ba29c632bd4aa7d31072a84693
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Somasundaram, RajeshÅhsberg, JosefineOkuyama, KazukiUngerbäck, JonasStrid, TobiasSigvardsson, Mikael
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 43 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 83 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf