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

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Persistent malignant stem cells in del(5q) myelodysplasia in remission. / Tehranchi, Ramin; Woll, Petter S; Anderson, Kristina; Buza-Vidas, Natalija; Mizukami, Takuo; Mead, Adam J; Åstrand-Grundström, Ingbritt; Strömbeck, Bodil; Biloglav, Andrea; Ferry, Helen; Dhanda, Rakesh Singh; Hast, Robert; Rydén, Tobias; Vyas, Paresh; Göhring, Gudrun; Schlegelberger, Brigitte; Johansson, Bertil; Hellström, Eva; List, Alan; Nilsson, Lars; Jacobsen, Sten Eirik W.

I: New England Journal of Medicine, Vol. 363, Nr. 11, 2010, s. 1025-1037.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Tehranchi, R, Woll, PS, Anderson, K, Buza-Vidas, N, Mizukami, T, Mead, AJ, Åstrand-Grundström, I, Strömbeck, B, Biloglav, A, Ferry, H, Dhanda, RS, Hast, R, Rydén, T, Vyas, P, Göhring, G, Schlegelberger, B, Johansson, B, Hellström, E, List, A, Nilsson, L & Jacobsen, SEW 2010, 'Persistent malignant stem cells in del(5q) myelodysplasia in remission.', New England Journal of Medicine, vol. 363, nr. 11, s. 1025-1037. https://doi.org/10.1056/NEJMoa0912228

APA

Tehranchi, R., Woll, P. S., Anderson, K., Buza-Vidas, N., Mizukami, T., Mead, A. J., Åstrand-Grundström, I., Strömbeck, B., Biloglav, A., Ferry, H., Dhanda, R. S., Hast, R., Rydén, T., Vyas, P., Göhring, G., Schlegelberger, B., Johansson, B., Hellström, E., List, A., ... Jacobsen, S. E. W. (2010). Persistent malignant stem cells in del(5q) myelodysplasia in remission. New England Journal of Medicine, 363(11), 1025-1037. https://doi.org/10.1056/NEJMoa0912228

CBE

Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, Åstrand-Grundström I, Strömbeck B, Biloglav A, Ferry H, Dhanda RS, Hast R, Rydén T, Vyas P, Göhring G, Schlegelberger B, Johansson B, Hellström E, List A, Nilsson L, Jacobsen SEW. 2010. Persistent malignant stem cells in del(5q) myelodysplasia in remission. New England Journal of Medicine. 363(11):1025-1037. https://doi.org/10.1056/NEJMoa0912228

MLA

Vancouver

Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ et al. Persistent malignant stem cells in del(5q) myelodysplasia in remission. New England Journal of Medicine. 2010;363(11):1025-1037. https://doi.org/10.1056/NEJMoa0912228

Author

Tehranchi, Ramin ; Woll, Petter S ; Anderson, Kristina ; Buza-Vidas, Natalija ; Mizukami, Takuo ; Mead, Adam J ; Åstrand-Grundström, Ingbritt ; Strömbeck, Bodil ; Biloglav, Andrea ; Ferry, Helen ; Dhanda, Rakesh Singh ; Hast, Robert ; Rydén, Tobias ; Vyas, Paresh ; Göhring, Gudrun ; Schlegelberger, Brigitte ; Johansson, Bertil ; Hellström, Eva ; List, Alan ; Nilsson, Lars ; Jacobsen, Sten Eirik W. / Persistent malignant stem cells in del(5q) myelodysplasia in remission. I: New England Journal of Medicine. 2010 ; Vol. 363, Nr. 11. s. 1025-1037.

RIS

TY - JOUR

T1 - Persistent malignant stem cells in del(5q) myelodysplasia in remission.

AU - Tehranchi, Ramin

AU - Woll, Petter S

AU - Anderson, Kristina

AU - Buza-Vidas, Natalija

AU - Mizukami, Takuo

AU - Mead, Adam J

AU - Åstrand-Grundström, Ingbritt

AU - Strömbeck, Bodil

AU - Biloglav, Andrea

AU - Ferry, Helen

AU - Dhanda, Rakesh Singh

AU - Hast, Robert

AU - Rydén, Tobias

AU - Vyas, Paresh

AU - Göhring, Gudrun

AU - Schlegelberger, Brigitte

AU - Johansson, Bertil

AU - Hellström, Eva

AU - List, Alan

AU - Nilsson, Lars

AU - Jacobsen, Sten Eirik W

PY - 2010

Y1 - 2010

N2 - 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.)

AB - 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.)

KW - Myelodysplastic Syndromes: genetics

KW - Myelodysplastic Syndromes: drug therapy

KW - Drug Resistance: genetics

KW - Pair 5: genetics

KW - Human

KW - Chromosomes

KW - Antineoplastic Agents: therapeutic use

KW - Antineoplastic Agents: pharmacology

KW - Thy-1: analysis

KW - Antigens

KW - CD34: analysis

KW - CD38: analysis

KW - Thalidomide: pharmacology

KW - Thalidomide: therapeutic use

KW - Thalidomide: analogs & derivatives

KW - Neoplastic Stem Cells: immunology

KW - Neoplastic Stem Cells: drug effects

KW - Myelodysplastic Syndromes: pathology

U2 - 10.1056/NEJMoa0912228

DO - 10.1056/NEJMoa0912228

M3 - Article

C2 - 20825315

VL - 363

SP - 1025

EP - 1037

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 11

ER -