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.
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.
Département de Génétique, UF de Génétique Moléculaire, Hôpital Robert Debré, APHP, Paris, France.
Aurélie
A
Caye
Kheïra
K
Beldjord
Kelly
K
Mass-Malo
Séverine
S
Drunat
Jean
J
Soulier
Virginie
V
Gandemer
André
A
Baruchel
Yves
Y
Bertrand
Hélène
H
Cavé
Emmanuelle
E
Clappier
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D021901:DNA, Intergenic / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D018365:Neoplasm, Residual / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017384:Sequence Deletion
D021901:DNA, Intergenic; C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor