SH2B3 aberrations enriched in iAMP21 B lymphoblastic leukemia.
Cancer Genet
; 226-227: 30-35, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30005852
ABSTRACT
Acute lymphoblastic leukemia (ALL) represents the most common childhood malignancy. Although survival for pediatric B-ALL has approached 90%, variability in outcome among and within cytogenetically defined subgroups persists. While G-banding and fluorescence in situ hybridization (FISH) have been used to characterize leukemic clones, there is added value of chromosomal microarray and next generation sequencing in screening genome-wide for copy number aberrations, copy neutral loss of heterozygosity and nucleotide variations. Evaluation of novel genetic aberrations can provide information about the biologic mechanisms of cytogenetically defined subgroups associated with poor prognosis, explain heterogeneity in patient outcome and identify novel targets for therapeutic intervention. The high risk B-ALL intrachromosomal amplification of chromosome 21, (iAMP21), subtype is characterized by amplification of a region of chromosome 21 that typically encompasses the RUNX1 gene and is associated with poor prognosis. Analysis of chromosomal microarray and FISH data revealed that deletions of SH2B3, encoding a negative regulator of multiple tyrosine kinase and cytokine signaling pathways, are enriched among leukemias harboring iAMP21. Enrichment of SH2B3 aberrations in the iAMP21 subtype may indicate that loss of SH2B3 contributes to disease progression and raises the possibility that these leukemias may be sensitive to tyrosine kinase inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 21
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Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Proteínas
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Amplificação de Genes
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Mutação
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Cancer Genet
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos