Treatment-influenced associations of PML-RARα mutations, FLT3 mutations, and additional chromosome abnormalities in relapsed acute promyelocytic leukemia.
Blood
; 120(10): 2098-108, 2012 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-22734072
ABSTRACT
Mutations in the all-trans retinoic acid (ATRA)-targeted ligand binding domain of PML-RARα (PRα/LBD+) have been implicated in the passive selection of ATRA-resistant acute promyelocytic leukemia clones leading to disease relapse. Among 45 relapse patients from the ATRA/chemotherapy arm of intergroup protocol C9710, 18 patients harbored PRα/LBD+ (40%), 7 of whom (39%) relapsed Off-ATRA selection pressure, suggesting a possible active role of PRα/LBD+. Of 41 relapse patients coanalyzed, 15 (37%) had FMS-related tyrosine kinase 3 internal tandem duplication mutations (FLT3-ITD+), which were differentially associated with PRα/LBD+ depending on ATRA treatment status at relapse positively, On-ATRA; negatively, Off-ATRA. Thirteen of 21 patients (62%) had additional chromosome abnormalities (ACAs); all coanalyzed PRα/LBD mutant patients who relapsed off-ATRA (n = 5) had associated ACA. After relapse Off-ATRA, ACA and FLT3-ITD+ were negatively associated and were oppositely associated with presenting white blood count and PML-RARα type ACA, low, L-isoform; FLT3-ITD+, high, S-isoform. These exploratory results suggest that differing PRα/LBD+ activities may interact with FLT3-ITD+ or ACA, that FLT3-ITD+ and ACA are associated with different intrinsic disease progression pathways manifest at relapse Off-ATRA, and that these different pathways may be short-circuited by ATRA-selectable defects at relapse On-ATRA. ACA and certain PRα/LBD+ were also associated with reduced postrelapse survival.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Leucemia Promielocítica Aguda
/
Proteínas de Fusão Oncogênica
/
Aberrações Cromossômicas
/
Tirosina Quinase 3 Semelhante a fms
/
Antineoplásicos
Tipo de estudo:
Guideline
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Humans
/
Infant
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article