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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.

Original publication




Journal article



Publication Date





1762 - 1766


Aged, Antineoplastic Agents, Bone Marrow Cells, Chromosome Banding, Chromosome Deletion, Chromosomes, Human, Pair 5, Clone Cells, Disease Progression, Female, Gene Expression Profiling, Genetic Heterogeneity, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Lenalidomide, Mutation, Myelodysplastic Syndromes, Thalidomide, Tumor Suppressor Protein p53