title: Persistent malignant stem cells in del(5q) myelodysplasia in remission.
abstract: 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.affiliation: Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Ramin
authors.initials: R
authors.lastname: Tehranchi
authors.forename: Petter S
authors.initials: PS
authors.lastname: Woll
authors.forename: Kristina
authors.initials: K
authors.lastname: Anderson
authors.forename: Natalija
authors.initials: N
authors.lastname: Buza-Vidas
authors.forename: Takuo
authors.initials: T
authors.lastname: Mizukami
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Mead
authors.forename: Ingbritt
authors.initials: I
authors.lastname: Astrand-Grundström
authors.forename: Bodil
authors.initials: B
authors.lastname: Strömbeck
authors.forename: Andrea
authors.initials: A
authors.lastname: Horvat
authors.forename: Helen
authors.initials: H
authors.lastname: Ferry
authors.forename: Rakesh Singh
authors.initials: RS
authors.lastname: Dhanda
authors.forename: Robert
authors.initials: R
authors.lastname: Hast
authors.forename: Tobias
authors.initials: T
authors.lastname: Rydén
authors.forename: Paresh
authors.initials: P
authors.lastname: Vyas
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: Alan
authors.initials: A
authors.lastname: List
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D012074:Remission Induction; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018800:Thy-1 Antigens / Q000032:analysis
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D018800:Thy-1 Antigens; D013792:Thalidomide; D051997:ADP-ribosyl Cyclase 1; D000077269:Lenalidomide