Prognostic utility of key copy number alterations in T cell acute lymphoblastic leukemia.
CDKN2A/B
MLPA
T-ALL
copy number alterations
leukemia
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
revised:
26
04
2022
received:
05
02
2022
accepted:
21
05
2022
pubmed:
2
6
2022
medline:
12
10
2022
entrez:
1
6
2022
Statut:
ppublish
Résumé
T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease, characterized by an abnormal transformation of T cells into highly proliferative leukemic lymphoblasts. Identification of common genetic alterations has provided promising opportunities for better risk stratification in T-ALL. Current treatment in T-ALL still poses the major challenge of integrating the knowledge of molecular alterations in the clinical setting. We utilized the Multiplex Ligation Dependent Probe Amplification (MLPA) method to determine the frequency of common copy number alterations (CNAs) in 128 newly diagnosed T-ALL patients. We also studied the association of these CNAs with patient's clinical characteristics and survival. The highest frequency of deletion was observed in CDKN2A (59.38%), followed by CDKN2B (46.88%), LMO1 (37.5%), and MTAP (28.12%). PTPN2 (22.66%), PHF6 (14.06%), and MYB (14.06%) had the highest number of duplication events. A total of 89.06% patients exhibited CNAs. STIL::TAL1, NUP214::ABL1, and LMO2::RAG2 fusions were observed in 5.47%, 3.12%, and 0.78% of patients, respectively. CDKN2A, CDKN2B, and PTPN2 gene deletions were mainly observed in pediatric patients, while CNAs of NF1 and SUZ12 were observed more frequently in adults. In pediatric patients, alterations in CDKN2B, CASP8AP2, and AHI1 were associated with poor prognosis, while SUZ12 and NF1 CNAs were associated with favorable prognosis. In adult patients, ABL1 CNA emerged as an independent indicator of poor prognosis. The observed molecular heterogeneity in T-ALL may provide the basis for variations observed in clinical response in T-ALL and MLPA based CNA detection may help in risk stratification of these patients.
Substances chimiques
Protein Tyrosine Phosphatase, Non-Receptor Type 2
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
577-587Subventions
Organisme : Department of Science and Technology, Ministry of Science and Technology, India
Organisme : The Wellcome Trust DBT India Alliance
Informations de copyright
© 2022 John Wiley & Sons Ltd.
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