| Title: |
14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia |
| Authors: |
Di Giacomo D.; La Starza R.; Gorello P.; Pellanera F.; Kalender Atak Z.; De Keersmaecker K.; Pierini V.; Harrison C. J.; Arniani S.; Moretti M.; Testoni N.; De Santis G.; Roti G.; Matteucci C.; Bassan R.; Vandenberghe P.; Aerts S.; Cools J.; Bornhauser B.; Bourquin J. -P.; Piazza R.; Mecucci C. |
| Contributors: |
Di Giacomo, D.; La Starza, R.; Gorello, P.; Pellanera, F.; Kalender Atak, Z.; De Keersmaecker, K.; Pierini, V.; Harrison, C. J.; Arniani, S.; Moretti, M.; Testoni, N.; De Santis, G.; Roti, G.; Matteucci, C.; Bassan, R.; Vandenberghe, P.; Aerts, S.; Cools, J.; Bornhauser, B.; Bourquin, J. -P.; Piazza, R.; Mecucci, C. |
| Publication Year: |
2021 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
Adolescent; Adult; Aged; Child; Preschool; Chromosomes; Human; Pair 14; Female; Gene Expression Profiling; Male; Middle Aged; Biomarkers; Tumor; Gene Expression Regulation; Leukemic; Leukemia; Myeloid; Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Repressor Protein; Translocation; Genetic; Tumor Suppressor Proteins |
| Description: |
Acute leukemias (ALs) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by coexpression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML, M0 or M1), T/myeloid mixed-phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell acute lymphoblastic leukemias (T-ALL: 58, ETP; 178, non-ETP; 8, T/M MPAL; 89, not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3.6% of T-ALL), harboring 4 types of 14q32/BCL11B translocations: t(2,14)(q22.3;q32) (n = 7), t(6;14)(q25.3;q32) (n = 9), t(7;14)(q21.2;q32) (n = 2), and t(8;14)(q24.2;q32) (n = 2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, whereas the other 3 rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker that was present at diagnosis, but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently the DNMT3A, TET2, and/or WT1 genes. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B AL from AML, T-ALL, and ETP-ALL. Remarkably, an ex vivo drug-sensitivity profile identified a panel of compounds with effective antileukemic activity. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/33876209; info:eu-repo/semantics/altIdentifier/wos/WOS:000692441100007; volume:138; issue:9; firstpage:773; lastpage:784; numberofpages:12; journal:BLOOD; https://hdl.handle.net/11585/866960 |
| DOI: |
10.1182/blood.2020010510 |
| Availability: |
https://hdl.handle.net/11585/866960; https://doi.org/10.1182/blood.2020010510; https://ashpublications.org/blood/article/138/9/773/475778/14q32-rearrangements-deregulating-BCL11B-mark-a |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.A2F418B4 |
| Database: |
BASE |