1. 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
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Aurélie Caye, Emmanuelle Clappier, Yves Bertrand, Jean Soulier, André Baruchel, Kheira Beldjord, Hélène Cavé, Kelly Mass-Malo, Virginie Gandemer, Séverine Drunat, Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine de l'enfant et de l'adolescent, CHU Pontchaillou [Rennes]-Hôpital Sud, Service d'hématologie et immunologie pédiatrique, Service de pédiatrie, Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Université Paris Diderot - Paris 7 (UPD7), Service de Biochimie Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes]-hôpital Sud, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré
- Subjects
Male ,Neoplasm, Residual ,Cohort Studies ,Chromosome Breakpoints ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Child ,Sequence Deletion ,Chromosome 7 (human) ,Genetics ,Comparative Genomic Hybridization ,0303 health sciences ,Chromosome Mapping ,Hematology ,Prognosis ,Ikaros Transcription Factor ,3. Good health ,medicine.anatomical_structure ,Residual ,Child, Preschool ,030220 oncology & carcinogenesis ,Pair 7 ,DNA, Intergenic ,Female ,Chromosomes, Human, Pair 7 ,Human ,Adolescent ,Biology ,Sensitivity and Specificity ,Chromosomes ,03 medical and health sciences ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Multiplex polymerase chain reaction ,medicine ,Humans ,Genetic Testing ,Preschool ,B cell ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Intergenic ,Breakpoint ,Infant ,Reproducibility of Results ,DNA ,Minimal residual disease ,Neoplasm ,Original Articles and Brief Reports ,Multiplex Polymerase Chain Reaction ,Comparative genomic hybridization - Abstract
International audience; 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.
- Published
- 2012
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