Open AccessMyeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes
Author(s) -
Parinet Vincent,
Chapiro Elise,
Bidet Audrey,
Gaillard Baptiste,
Maarek Odile,
Simon Laurence,
Lefebvre Christine,
Defasque Sabine,
Mozziconacci MarieJoelle,
Quinquenel Anne,
Decamp Matthieu,
Lifermann François,
AliAmmar Nadia,
Maillon Agathe,
Baron Marine,
Martin Mélanie,
Struski Stéphanie,
Penther Dominique,
Micol JeanBaptiste,
Auger Nathalie,
BilhouNabera Chrystèle,
Martignoles JeanAlain,
Tondeur Sylvie,
NguyenKhac Florence,
Hirsch Pierre,
RoosWeil Damien
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16895
Subject(s) - etv6 , chromosomal translocation , cebpa , myelodysplastic syndromes , medicine , dysplasia , idh1 , myeloid , oncology , biology , runx1 , gastroenterology , cancer research , mutation , bone marrow , gene , genetics , haematopoiesis , stem cell
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.