Progression in patients with low- and intermediate-1-risk del(5q) myelodysplastic syndromes is predicted by a limited subset of mutations

Haematologica. 2017 Mar;102(3):498-508. doi: 10.3324/haematol.2016.152025. Epub 2016 Nov 24.


A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes will respond to treatment with lenalidomide. The median duration of transfusion-independence is 2 years with some long-lasting responses, but almost 40% of patients progress to acute leukemia by 5 years after starting treatment. The mechanisms underlying disease progression other than the well-established finding of small TP53-mutated subclones at diagnosis remain unclear. We studied a longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of hematopoietic stem and progenitor cell subsets, targeted sequencing of mutational patterns, and changes in the bone marrow microenvironment. All 13 patients with disease progression were identified by a limited number of mutations in TP53, RUNX1, and TET2, respectively, with PTPN11 and SF3B1 occurring in one patient each. TP53 mutations were found in seven of nine patients who developed acute leukemia, and were documented to be present in the earliest sample (n=1) and acquired during lenalidomide treatment (n=6). By contrast, analysis of the microenvironment, and of hematopoietic stem and progenitor cells by flow cytometry was of limited prognostic value. Based on our data, we advocate conducting a prospective study aimed at investigating, in a larger number of cases of del(5q) myelodysplastic syndromes, whether the detection of such mutations before and after lenalidomide treatment can guide clinical decision-making.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 5*
  • Computational Biology / methods
  • Disease Progression
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Lenalidomide
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / therapy
  • Prognosis
  • Stem Cell Niche
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Treatment Outcome


  • Biomarkers
  • Thalidomide
  • Lenalidomide