Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression.
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 res...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1826299368009891840 |
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| author | Jädersten, M Saft, L Pellagatti, A Göhring, G Wainscoat, J Boultwood, J Porwit, A Schlegelberger, B Hellström-Lindberg, E |
| author_facet | Jädersten, M Saft, L Pellagatti, A Göhring, G Wainscoat, J Boultwood, J Porwit, A Schlegelberger, B Hellström-Lindberg, E |
| author_sort | Jädersten, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:00:53Z |
| format | Journal article |
| id | oxford-uuid:d83fce16-3954-4977-bcaf-352d28fc1c8b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:00:53Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:d83fce16-3954-4977-bcaf-352d28fc1c8b2022-03-27T08:46:55ZClonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d83fce16-3954-4977-bcaf-352d28fc1c8bEnglishSymplectic Elements at Oxford2009Jädersten, MSaft, LPellagatti, AGöhring, GWainscoat, JBoultwood, JPorwit, ASchlegelberger, BHellström-Lindberg, EClonal 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. |
| spellingShingle | Jädersten, M Saft, L Pellagatti, A Göhring, G Wainscoat, J Boultwood, J Porwit, A Schlegelberger, B Hellström-Lindberg, E Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title | Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title_full | Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title_fullStr | Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title_full_unstemmed | Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title_short | Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. |
| title_sort | clonal heterogeneity in the 5q syndrome p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression |
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