FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact
| Autor: | Chor S. Chim, Raymond Liang, Edmond S. K. Ma, Albert K. W. Lie, A. Fung, Kit Fai Wong, Yok L. Kwong, Wing Y. Au, Cheuk H. Chan |
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| Rok vydání: | 2004 |
| Předmět: |
Oncology
medicine.medical_specialty medicine.disease_cause law.invention Exon law Internal medicine White blood cell medicine Survival rate Polymerase chain reaction Mutation Hematology business.industry medicine.disease body regions Leukemia medicine.anatomical_structure Immunology Cohort cardiovascular system sense organs business psychological phenomena and processes circulatory and respiratory physiology |
| Zdroj: | British Journal of Haematology. 125:463-469 |
| ISSN: | 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2004.04935.x |
| Popis: | FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 ITD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL. |
| Databáze: | OpenAIRE |
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