Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression

Haematologica. 2009 Dec;94(12):1762-6. doi: 10.3324/haematol.2009.011528. Epub 2009 Oct 1.


Clonal heterogeneity has not been described in patients with myelodysplastic syndrome with isolated del(5q), for which lenalidomide has emerged as a highly potent treatment. However, transformation to acute myeloid leukemia is occasionally observed, particularly in patients without a cytogenetic response to lenalidomide. We performed molecular studies in a patient with classical 5q- syndrome with complete erythroid and partial cytogenetic response to lenalidomide, who evolved to high-risk myelodysplastic syndrome with complex karyotype. Immunohistochemistry of pre-treatment marrow biopsies revealed a small fraction of progenitors with overexpression of p53 and sequencing confirmed a TP53 mutation. TP53 mutated subclones have not previously been described in myelodysplastic syndrome with isolated del(5q) and indicates a previously unknown heterogeneity of this disease. The aberrant subclone remained stable during the treatment with lenalidomide and expanded at transformation, suggesting that this pre-existing cell population had molecular features which made it insensitive to lenalidomide and prone to disease progression.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Chromosome Banding
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 5 / genetics*
  • Clone Cells / metabolism
  • Clone Cells / pathology
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Genetic Heterogeneity
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Lenalidomide
  • Mutation
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Tumor Suppressor Protein p53 / genetics


  • Antineoplastic Agents
  • Tumor Suppressor Protein p53
  • Thalidomide
  • Lenalidomide