Breakpoint-specific multiplex polymerase chain reaction allows the detection of IKZF1 intragenic deletions and minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia
Résumé
Deletion of the Ikaros (IKZF1) gene is an oncogenic lesion frequently associated with BCR-ABL1-positive acute lymphoblastic leukemias. It is also found in a fraction of BCR-ABL1-negative B-cell precursor acute lymphoblastic leukemias, and early studies showed it was associated with a higher risk of relapse. Therefore, screening tools are needed for evaluation in treatment protocols and possible inclusion in risk stratification. Besides monosomy 7 and large 7p abnormalities encompassing IKZF1, most IKZF1 alterations are short, intragenic deletions. Based on cohorts of patients, we mapped the microdeletion breakpoints and developed a breakpoint-specific fluorescent multiplex polymerase chain reaction that allows detection of recurrent intragenic deletions. This sensitive test could also detect IKZF1 subclonal deletions, whose prognostic significance should be evaluated. Moreover, we show that consensus breakpoint sequences can be used as clonal markers to monitor minimal residual disease. This paper could be useful for translational studies and in clinical management of BCP-ALL.
Mots clés
Adolescent
Child
Preschool
Chromosome Breakpoints
Chromosome Mapping
Chromosomes
Human
Pair 7
Cohort Studies
Comparative Genomic Hybridization
DNA
Intergenic
Female
Genetic Testing
Humans
Ikaros Transcription Factor
Infant
Male
Multiplex Polymerase Chain Reaction
Neoplasm
Residual
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Reproducibility of Results
Risk Factors
Sensitivity and Specificity
Sequence Deletion