title: Gene copy number alteration profile and its clinical correlation in B-cell acute lymphoblastic leukemia.
abstract: The genes related to B-cell development are frequently altered in B-cell acute lymphoblastic leukemia (B-ALL). One hundred sixty-two newly diagnosed B-ALL cases, median age 8.5 years (2 months-67 years), were prospectively analyzed for copy number alterations (CNAs) in CDKN2A/B, IKZF1, PAX5, RB1, ETV6, BTG1, EBF1, and pseudoautosomal region genes (CRLF2, CSF2RA, IL3RA) using multiplex ligation-dependent probe amplification. The CNAs were detected in 114 (70.4%) cases; most commonly affected genes being CDKN2A/B-55 (34%), PAX5-51 (31.5%), and IKZF1-43 (26.5%). IKZF1 and RB1 deletions correlated with higher induction failure. Patients classified as good-risk, according to the integrated CNA profile and cytogenetic criteria, had lower induction failure [5 (8.6%) vs. 20 (25.3%); p = 0.012]. Those classified as good-risk, based on CNA profile irrespective of cytogenetics, also showed lower induction failure [6 (9.4%) vs. 19 (26%); p = 0.012]. The CNA profile identified patients with better induction outcome and has a potential role in better risk stratification of B-ALL.
authors.affiliation: a Lab Oncology Unit, Dr BRA IRCH , All India Institute of Medical Sciences (AIIMS) , New Delhi , India.
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: b Department of Medical Oncology, Dr BRA IRCH , All India Institute of Medical Sciences (AIIMS) , New Delhi , India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
authors.affiliation: b Department of Medical Oncology, Dr BRA IRCH , All India Institute of Medical Sciences (AIIMS) , New Delhi , India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.affiliation: c Department of Biostatistics , All India Institute of Medical Sciences (AIIMS) , New Delhi , India.
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Kamal
authors.affiliation: a Lab Oncology Unit, Dr BRA IRCH , All India Institute of Medical Sciences (AIIMS) , New Delhi , India.
authors.forename: Rajive
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
keywords: B-ALL genetics; MLPA in B-ALL; copy number variations in ALL; mutations in acute leukemia