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Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia

Lookup NU author(s): Claire Schwab, Professor Christine Harrison

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Abstract

Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up-and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia.


Publication metadata

Author(s): La Starza R, Barba G, Demeyer S, Pierini V, Di Giacomo D, Gianfelici V, Schwab C, Matteucci C, Vicente C, Cools J, Messina M, Crescenzi B, Chiaretti S, Foà R, Basso G, Harrison CJ, Mecucci C

Publication type: Article

Publication status: Published

Journal: Haematologica

Year: 2016

Volume: 101

Issue: 8

Pages: 951-958

Print publication date: 01/08/2016

Online publication date: 01/05/2016

Acceptance date: 29/04/2016

ISSN (print): 0390-6078

ISSN (electronic): 1592-8721

Publisher: Fondazione Ferrata Storti

URL: http://dx.doi.org/10.3324/haematol.2016.143875

DOI: 10.3324/haematol.2016.143875

PubMed id: 27151989


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