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Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia

Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia
Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia
Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults.
infant, t-cell acute lymphoblastic leukaemaia, enomic profile, cnas and in utero origin
0007-1048
574-584
Mansur, Marcela B.
74202914-7d77-4436-9c79-8c14e16a1214
van Delft, Frederik W.
4a8800c6-f241-4efd-a3bc-23f6e37d3b21
Colman, Susan M.
b2206191-bf7e-4d68-b735-9556af874cb6
Furness, Caroline L.
7eb6b6e7-23de-411d-a0c1-8f4e2446559c
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Emerenciano, Mariana
2eec72b7-b15a-446a-8333-4093270a4e8b
Kempski, Helena
a2db8f50-62b6-4baf-92a8-767f40a2563a
Clappier, Emmanuelle
c8270907-eb65-4775-a1b0-27cebd657f88
Cave, Hélène
5b89bd67-8373-4766-be76-ff9195be227c
Soulier, Jean
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Pombo-de-Oliveira, Maria S.
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Greaves, Mel
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Ford, Anthony M.
169874bf-aa5d-4f7d-ba15-037098cce1dc
Mansur, Marcela B.
74202914-7d77-4436-9c79-8c14e16a1214
van Delft, Frederik W.
4a8800c6-f241-4efd-a3bc-23f6e37d3b21
Colman, Susan M.
b2206191-bf7e-4d68-b735-9556af874cb6
Furness, Caroline L.
7eb6b6e7-23de-411d-a0c1-8f4e2446559c
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Emerenciano, Mariana
2eec72b7-b15a-446a-8333-4093270a4e8b
Kempski, Helena
a2db8f50-62b6-4baf-92a8-767f40a2563a
Clappier, Emmanuelle
c8270907-eb65-4775-a1b0-27cebd657f88
Cave, Hélène
5b89bd67-8373-4766-be76-ff9195be227c
Soulier, Jean
66135546-7153-4e90-8374-c710f799c5c1
Pombo-de-Oliveira, Maria S.
09e1271b-c866-4de1-b3e6-3a72ac6519db
Greaves, Mel
3e423ea6-a6e0-4b97-b8d6-26993d34ec88
Ford, Anthony M.
169874bf-aa5d-4f7d-ba15-037098cce1dc

Mansur, Marcela B., van Delft, Frederik W. and Colman, Susan M. et al. (2015) Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia. British Journal of Haematology, 171 (4), 574-584. (doi:10.1111/bjh.13613). (PMID:26205622)

Record type: Article

Abstract

Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults.

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More information

Accepted/In Press date: 25 June 2015
e-pub ahead of print date: 24 July 2015
Published date: 29 October 2015
Keywords: infant, t-cell acute lymphoblastic leukaemaia, enomic profile, cnas and in utero origin
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 383503
URI: http://eprints.soton.ac.uk/id/eprint/383503
ISSN: 0007-1048
PURE UUID: 6c169c59-73ff-432c-9a82-305d45c480cc
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285

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Date deposited: 17 Nov 2015 14:20
Last modified: 15 Mar 2024 03:17

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Contributors

Author: Marcela B. Mansur
Author: Frederik W. van Delft
Author: Susan M. Colman
Author: Caroline L. Furness
Author: Jane Gibson ORCID iD
Author: Mariana Emerenciano
Author: Helena Kempski
Author: Emmanuelle Clappier
Author: Hélène Cave
Author: Jean Soulier
Author: Maria S. Pombo-de-Oliveira
Author: Mel Greaves
Author: Anthony M. Ford

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