The RS4;11 cell line as a model for leukaemia with t(4;11)(q21;q23): Revised characterisation of cytogenetic features.
Cancer Rep (Hoboken)
; 2(5): e1207, 2019 10.
Article
de En
| MEDLINE
| ID: mdl-32721124
ABSTRACT
BACKGROUND:
Haematological malignancies harbouring rearrangements of the KMT2A gene represent a unique subtype of leukaemia, with biphenotypic clinical manifestations, a rapid and aggressive onset, and a generally poor prognosis. Chromosomal translocations involving KMT2A often cause the formation of oncogenic fusion genes, such as the most common translocation t(4;11)(q21;q23) producing the KMT2A-AFF1 chimera.AIM:
The aim of this study was to confirm and review the cytogenetic and molecular features of the KMT2A-rearranged RS4;11 cell line and put those in context with other reports of cell lines also harbouring a t(4;11) rearrangement. METHODS ANDRESULTS:
The main chromosomal rearrangements t(4;11)(q21;q23) and i(7q), described when the cell line was first established, were confirmed by fluorescence in situ hybridisation (FISH) and 24-colour karyotyping by M-FISH. Additional cytogenetic abnormalities were investigated by further FISH experiments, including the presence of trisomy 18 as a clonal abnormality and the discovery of one chromosome 8 being an i(8q), which indicates a duplication of the oncogene MYC. A homozygous deletion of 9p21 containing the tumour-suppressor genes CDKN2A and CDKN2B was also revealed by FISH. The production of the fusion transcript KMT2A-AFF1 arising from the der(11)t(4;11) was confirmed by RT-PCR, but sequencing of the amplified fragment revealed the presence of multiple isoforms. Two transcript variants, resulting from alternative splicing, were identified differing in one glutamine residue in the translated protein.CONCLUSION:
As karyotype evolution is a common issue in cell lines, we highlight the need to monitor cell lines in order to re-confirm their characteristics over time. We also reviewed the literature to provide a comparison of key features of several cell lines harbouring a t(4;11). This would guide scientists in selecting the most suitable research model for this particular type of KMT2A-leukaemia.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Leucémies
/
Protéines de fusion oncogènes
/
Histone-lysine N-methyltransferase
/
Facteurs d'élongation transcriptionnelle
/
Protéines de liaison à l'ADN
/
Protéine de la leucémie myéloïde-lymphoïde
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Cancer Rep (Hoboken)
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni