دورية أكاديمية
14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia
| العنوان: | 14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia |
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| المؤلفون: | 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. |
| المساهمون: | 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. |
| بيانات النشر: | Elsevier B.V. |
| سنة النشر: | 2021 |
| المجموعة: | Università di Parma: CINECA IRIS |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000692441100007; volume:138; issue:9; firstpage:773; lastpage:784; numberofpages:12; journal:BLOOD; http://hdl.handle.net/11381/2907602Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85111465916 |
| DOI: | 10.1182/blood.2020010510 |
| الإتاحة: | https://doi.org/10.1182/blood.2020010510Test http://hdl.handle.net/11381/2907602Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.C93431BF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/blood.2020010510 |
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