title: Concordant B-cell precursor acute lymphoblastic leukemia in non-twinned siblings.
abstract: Associating the risk of childhood acute lymphoblastic leukemia (ALL) with genetic predisposition is still a challenge. Here, we discuss two non-twinned sibs (girl and boy) diagnosed with B-cell precursor (BCP-ALL) and ETV6-RUNX1. BCP-ALL clinical onset occurred 10months apart from each diagnosis. One child is alive in complete continuous remission, whereas, the other relapsed and evolved to death with resistance to ALL treatment. Despite the fact that BCP-ALL with ETV6-RUNX1 usually results in a very good prognosis, the sibs experienced divergent outcomes; a remarkable difference in one child that presented a more aggressive disease was higher leukocytosis associated with IKZF1 deletion. The familial history of cancer and genetic susceptibility was explored. The sibs were absolutely identical in all 17 loci of genes tested; GSTM1, GSTT1, NQO1, TP53, and TP63 were wild-type, whereas at least one copy of the variant allele for IKZF1, ARID5B, PTPRJ and CEBPE was present. The familial pattern of ETV6 was tested by the 12p microsatellite analysis and demonstrated that deletions occurred in one child but not the other, while heterozygous patterns were found in the parents. Altogether, our data suggest that genetic predisposition aligned with chance haa an additive effect in BCP-ALL outcome.
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Rio de Janeiro, Brazil. Electronic address: mpombo@inca.gov.br.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.affiliation: Pediatric Hematology-Oncology Service, Hospital Joana de Gusmão, Florianópolis, Santa Catarina, Brazil.
authors.forename: Ana Paula Ferreira Freund
authors.initials: AP
authors.lastname: Winn
authors.affiliation: Pediatric Hematology-Oncology Service, Hospital Joana de Gusmão, Florianópolis, Santa Catarina, Brazil.
authors.forename: Imaruí
authors.initials: I
authors.lastname: Costa
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Marcela B
authors.initials: MB
authors.lastname: Mansur
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Ford
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D017353:Gene Deletion; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D035781:Siblings; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D051740:Ikaros Transcription Factor; D015514:Oncogene Proteins, Fusion; C497239:IKZF1 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein
keywords: B-cell precursor ALL; ETV6-RUNX1; Genetic-loci; Siblings