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  • Tehranchi, Ramin (author)

Persistent malignant stem cells in del(5q) myelodysplasia in remission.

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2010

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:89307a5f-3cce-4fea-b40f-e2a33e6f1182
  • https://lup.lub.lu.se/record/1688396URI
  • https://doi.org/10.1056/NEJMoa0912228DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-61158URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:121254549URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • QC 20120117
  • BACKGROUND: The in vivo clinical significance of malignant stem cells remains unclear. METHODS: Patients who have the 5q deletion (del[5q]) myelodysplastic syndrome (interstitial deletions involving the long arm of chromosome 5) have complete clinical and cytogenetic remissions in response to lenalidomide treatment, but they often have relapse. To determine whether the persistence of rare but distinct malignant stem cells accounts for such relapses, we examined bone marrow specimens obtained from seven patients with the del(5q) myelodysplastic syndrome who became transfusion-independent while receiving lenalidomide treatment and entered cytogenetic remission. RESULTS: Virtually all CD34+, CD38+ progenitor cells and stem cells that were positive for CD34 and CD90, with undetectable or low CD38 (CD38−/low), had the 5q deletion before treatment. Although lenalidomide efficiently reduced these progenitors in patients in complete remission, a larger fraction of the minor, quiescent, CD34+,CD38-/low, CD90+ del(5q) stem cells as well as functionally defined del(5q) stem cells remained distinctly resistant to lenalidomide. Over time, lenalidomide resistance developed in most of the patients in partial and complete remission, with recurrence or expansion of the del(5q) clone and clinical and cytogenetic progression. CONCLUSIONS: In these patients with the del(5q) myelodysplastic syndrome, we identified rare and phenotypically distinct del(5q) myelodysplastic syndrome stem cells that were also selectively resistant to therapeutic targeting at the time of complete clinical and cytogenetic remission. (Funded by the EuroCancerStemCell Consortium and others.)

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  • Woll, Petter S (author)
  • Anderson, Kristina (author)
  • Buza-Vidas, Natalija (author)
  • Mizukami, Takuo (author)
  • Mead, Adam J (author)
  • Åstrand-Grundström, IngbrittLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-iag (author)
  • Strömbeck, Bodil (author)
  • Biloglav, AndreaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)klin-aho (author)
  • Ferry, Helen (author)
  • Dhanda, Rakesh Singh (author)
  • Hast, RobertKarolinska Institutet (author)
  • Rydén, TobiasLund University(Swepub:kth)u1h50egr (author)
  • Vyas, Paresh (author)
  • Göhring, Gudrun (author)
  • Schlegelberger, Brigitte (author)
  • Johansson, BertilLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-bjo (author)
  • Hellström, EvaKarolinska Institutet (author)
  • List, Alan (author)
  • Nilsson, LarsLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-lni (author)
  • Jacobsen, Sten Eirik WKarolinska Institutet,Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)stem-sja (author)
  • Horvat, Andrea (author)
  • Stamcellscentrum (SCC)Avdelningen för stamcellsforskning (creator_code:org_t)

Related titles

  • In:New England Journal of Medicine363:11, s. 1025-10370028-47931533-4406

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