Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.
Adolescent
Adult
Aged
Aged, 80 and over
Blast Crisis
/ drug therapy
Blood Proteins
/ genetics
Clonal Evolution
/ genetics
Cohort Studies
Core Binding Factor Alpha 2 Subunit
/ genetics
Female
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Leukemia, Myeloid, Chronic-Phase
/ genetics
Male
Middle Aged
Mutation
Oncogene Proteins, Fusion
/ genetics
Prognosis
Protein Kinase Inhibitors
/ pharmacology
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Proto-Oncogene Protein c-ets-2
/ genetics
Exome Sequencing
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 05 2021
14 05 2021
Historique:
received:
18
09
2020
accepted:
15
04
2021
entrez:
15
5
2021
pubmed:
16
5
2021
medline:
4
6
2021
Statut:
epublish
Résumé
Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.
Identifiants
pubmed: 33990592
doi: 10.1038/s41467-021-23097-w
pii: 10.1038/s41467-021-23097-w
pmc: PMC8121838
doi:
Substances chimiques
Blood Proteins
0
Core Binding Factor Alpha 2 Subunit
0
ETS2 protein, human
0
NBEAL2 protein, human
0
Oncogene Proteins, Fusion
0
Protein Kinase Inhibitors
0
Proto-Oncogene Protein c-ets-2
0
RUNX1 protein, human
0
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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