| Persistent malignant stem cells in del(5q) myelodysplasia in remission. | |
| | |
MedLine Citation:
|
PMID: 20825315 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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.) |
| | |
Authors:
|
Ramin Tehranchi; Petter S Woll; Kristina Anderson; Natalija Buza-Vidas; Takuo Mizukami; Adam J Mead; Ingbritt Astrand-Grundström; Bodil Strömbeck; Andrea Horvat; Helen Ferry; Rakesh Singh Dhanda; Robert Hast; Tobias Rydén; Paresh Vyas; Gudrun Göhring; Brigitte Schlegelberger; Bertil Johansson; Eva Hellström-Lindberg; Alan List; Lars Nilsson; Sten Eirik W Jacobsen |
Related Documents
:
|
11700155 - Hypercoagulability syndromes. 11755105 - Duplication 8 [inv dup(8)(p12p23)] with macrocephaly. 9799305 - Otodental syndrome, oculo-facio-cardio-dental (ofcd) syndrome, and lobodontia: dental d... 18328215 - Netherton's syndrome: the importance of eyebrow hair. 22533665 - The association of leptin and c-reactive protein with the cardiovascular risk factors a... 16365865 - May-thurner syndrome (iliac vein compression) and thrombosis in adolescents. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The New England journal of medicine Volume: 363 ISSN: 1533-4406 ISO Abbreviation: N. Engl. J. Med. Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-09-09 Completed Date: 2010-09-21 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: United States |
Other Details:
|
Languages: eng Pagination: 1025-37 Citation Subset: AIM; IM |
Affiliation:
|
Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Lund, Sweden. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Aged, 80 and over Antigens, CD34 / analysis Antigens, CD38 / analysis Antigens, Thy-1 / analysis Antineoplastic Agents / pharmacology*, therapeutic use Chromosome Deletion* Chromosomes, Human, Pair 5 / genetics* Drug Resistance / genetics* Female Gene Expression Humans Male Middle Aged Myelodysplastic Syndromes / drug therapy, genetics, pathology* Neoplastic Stem Cells / drug effects*, immunology Phenotype Remission Induction Thalidomide / analogs & derivatives*, pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
//Medical Research Council |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD34; 0/Antigens, Thy-1; 0/Antineoplastic Agents; 191732-72-6/lenalidomide; 50-35-1/Thalidomide; EC 3.2.2.5/Antigens, CD38 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: E2-2 protein and Fuchs's corneal dystrophy.
Next Document: Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery.