A New Complex Karyotype Involving a KMT2A-r Variant Three-Way Translocation in a Rare Clinical Presentation of a Pediatric Patient with Acute Myeloid Leukemia
| Autor: | Moneeb A.K. Othman, Maria Luiza Macedo Silva, Gerson M. Ferreira, Isabel M. Carreira, Daniela R. Ney Garcia, Raul C. Ribeiro, Roberto R. Capela de Matos, Rolf Marschalek, Elaine Sobral da Costa, Marcelo Gerardin Poirot Land, Claus Meyer, Thomas Liehr, Joana B. Melo |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
biology Sequence analysis Childhood Acute Myeloid Leukemia Myeloid leukemia Karyotype Chromosomal translocation medicine.disease 03 medical and health sciences 0302 clinical medicine KMT2A 030220 oncology & carcinogenesis Complex Karyotype Genetics Myeloid sarcoma medicine biology.protein Cancer research Molecular Biology Genetics (clinical) 030304 developmental biology |
| Zdroj: | Cytogenetic and Genome Research. 157:213-219 |
| ISSN: | 1424-859X 1424-8581 |
| Popis: | Patients with childhood acute myeloid leukemia (AML) with complex karyotypes (CKs) have a dismal outcome. However, for patients with a KMT2A rearrangement (KMT2A-r), the prognosis appears to depend on the fusion partner gene rather than the karyotype structure. Thus, a precise characterization of KMT2A-r and the fusion partner genes, especially in CKs, is of interest for managing AML. We describe the clinical and molecular features of a child who presented with a large abdominal mass, AML, and a new CK, involving chromosomes 11, 16, and 19 leading to a KMT2A-MLLT1 fusion and 2 extra copies of the ELL gene, thus resulting in the concurrent overexpression of MLLT1 and ELL. Molecular cytogenetic studies defined the karyotype as 47,XY,der(11)t(11;16)(q23.3;p11.2),der(16)t(16;19)(p11.2;p13.3),der(19)t(11;19)(q23.3;p13.3),+der(19)t(16;19)(16pter→p11.2::19p13.3→19q11::19p11→19p13.3::16p11.2→16pter). Array CGH revealed a gain of 30.5 Mb in the 16p13.3p11.2 region and a gain of 18.1 Mb in the 19p13.3p12 region. LDI-PCR demonstrated the KMT2A-MLLT1 fusion. Reverse sequence analysis showed that the MLLT1 gene was fused to the 16p11.2 region. RT-qPCR quantification revealed that ELL and MLLT1 were overexpressed (4- and 10-fold, respectively). In summary, this is a pediatric case of AML presenting a novel complex t(11;16;19) variant with overexpression of ELL and MLLT1. |
| Databáze: | OpenAIRE |
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