Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia.
Haematologica
; 104(6): 1150-1155, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30573507
ABSTRACT
Clonal chromosome abnormalities in Philadelphia-negative cells could concern chronic myeloid leukemia patients treated by tyrosine kinase inhibitors. The European LeukemiaNet distinguishes -7/del(7q) abnormalities as a "warning". However, the impact of clonal chromosome abnormalities, and specifically those of -7/del(7q), in Philadelphia-negative cells on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome. The aim of this study was to determine whether the impact of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells on the clinical outcome is different from that of other types of abnormalities, and we argue for an underlying associated high-risk myelodysplastic syndrome. Among 102 chronic myeloid leukemia patients with clonal chromosome abnormalities in Philadelphia-negative cells with more than a median of 6 years of follow up, patients with -7/del(7q) more frequently had signs of dysplasia, a lower cumulative incidence of deep molecular response and often needed further treatment lines, with the consequent impact on event-free and progression-free survival. Morphological features of dysplasia are associated with myelodysplastic syndrome/acute myeloid leukemia mutations and compromise the optimal response to tyrosine kinase inhibitors, irrespectively of the type of clonal chromosome abnormalities in Philadelphia-negative cells. However, mutation patterns determined by next-generation sequencing could not clearly explain the underlying high-risk disease. We hereby confirm the pejorative prognostic value of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells and suggest that myelodysplastic features constitute a warning signal that response to tyrosine kinase inhibitors may be less than optimal.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Síndromes Mielodisplásicas
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Cromossomos Humanos Par 7
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Leucemia Mielogênica Crônica BCR-ABL Positiva
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Aberrações Cromossômicas
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Metáfase
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2019
Tipo de documento:
Article