Myeloid malignancies with translocation t(4;12)(q11-13;p13): molecular landscape, clonal hierarchy and clinical outcomes.
J Cell Mol Med
; 25(20): 9557-9566, 2021 10.
Article
in En
| MEDLINE
| ID: mdl-34492730
ABSTRACT
Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56-88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Translocation, Genetic
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Chromosomes, Human, Pair 4
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Chromosomes, Human, Pair 12
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Genetic Predisposition to Disease
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Myeloproliferative Disorders
Type of study:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limits:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
J Cell Mol Med
Year:
2021
Document type:
Article