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Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features

Lookup NU author(s): Claire Schwab, Dr Lucy Chilton, Heather Morrison, Lisa Jones, Dr Halima Al-shehhi, Dr Amy Erhorn, Dr Lisa Russell, Professor Anthony MoormanORCiD, Professor Christine Harrison FRCPath FMedSci

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Abstract

In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute lymphoblastic leukemia and the recently reported copy number abnormalities affecting significant leukemia associated genes. In a consecutive series of 1427 childhood B-cell precursor acute lymphoblastic leukemia patients, we have determined the incidence and type of copy number abnormalities using multiplex ligation-dependent probe amplification. We have shown strong links between certain deletions and cytogenetic subtypes, including the novel association between RB1 deletions and intrachromosomal amplification of chromosome 21. In this study, we characterized the different copy number abnormalities and show heterogeneity of PAX5 and IKZF1 deletions and the recurrent nature of RB1 deletions. Whole gene losses are often indicative of larger deletions, visible by conventional cytogenetics. An increased number of copy number abnormalities is associated with NCI high risk, specifically deletions of IKZF1 and CDKN2A/B, which occur more frequently among these patients. IKZF1 deletions and rearrangements of CRLF2 among patients with undefined karyotypes may point to the poor risk BCR-ABL1-like group. In conclusion, this study has demonstrated in a large representative cohort of children with B-cell precursor acute lymphoblastic leukemia that the pattern of copy number abnormalities is highly variable according to the primary genetic abnormality.

Publication metadata

Author(s): Schwab CJ, Chilton L, Morrison H, Jones L, Al-Shehhi H, Erhorn A, Russell LJ, Moorman AV, Harrison CJ

Publication type: Article

Publication status: Published

Journal: Haematologica

Year: 2013

Volume: 98

Issue: 7

Pages: 1081-1088

Print publication date: 18/03/2013

ISSN (print): 0390-6078

ISSN (electronic): 1592-8721

Publisher: Fondazione Ferrata Storti

URL: http://dx.doi.org/10.3324/haematol.2013.085175

DOI: 10.3324/haematol.2013.085175

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