t(1;19)(q22;p13.2) MEF2D/HNRNPUL1
2019-05-01 Tatiana Gindina Affiliation1.R.M. Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation at First Pavlov Saint-Petersburg State Medical University, Saint-Petersburg, Russia / [email protected]
Abstract
Review on t(1;19)(q22;p13.2), with data on the genes involved
Clinics and Pathology
Disease
B progenitor acute lymphoblastic leukemia.
Phenotype stem cell origin
The immunophenotype of MEF2D-rearranged ALL is characterized by weak or absent expression of CD10 and high expression of CD38, but these features are uncommon in B-cell precursor ALL (Gu et al., 2016).
Epidemiology
Only 8 cases to date (Gu et al., 2016; Lilljebjorn et al., 2016; Liu et al., 2016; Yasuda et al., 2016).
Prognosis
The outcome of MEF2D-rearranged ALL was inferior to that of other ALL subtypes (Gu et al., 2016).
Genes Involved and Proteins
Gene name
MEF2D (Myocyte Enhancer Factor 2D)
Location
1q22
Protein description
MEF2D belongs to the MADS-box family of transcription factors; this molecule binds as a homo- or hetero-dimer to the MEF2 element present in the regulatory regions of numerous muscle-specific and growth-factor and stress-induced genes. A remarkable increase in expression levels of MEF2A and MEF2D has been reported during differentiation into monocytes using the promyeloid HL-60 cell line (Yuki et al., 2004). In mouse models, MEF2D was identified as a candidate oncogene involved in the pathogenesis of leukemia. It is assumed, that native MEF2D has latent transforming properties, which can be unmasked via aberrant protein expression (Prima et al., 2005).
Gene name
HNRNPUL1 (Heterogeneous nuclear ribonucleoprotein U-like 1)
Location
19p13.2
Protein description
HNRNPUL1 is a nuclear RNA-binding protein which belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family. HNRNPUL1 acts as a basic transcriptional regulator and may exert a role in mRNA processing, nucleocytoplasmic RNA transport and DNA repair.
Result of the Chromosomal Anomaly
Description
The genes were fused in-frame between exon 8 of MEF2D and exon 12 of HNRNPUL1.The amino terminus of MEF2D was fused in frame with the carboxy-terminal portion of HNRNPUL1.
Oncogenesis
MEF2D/HNRNPUL1 fusion preserves the MEF2D MADS-box domain that mediates DNA binding and potentially dimerization. Thereby, aberrant function mediated by MEF2D transcriptional activation is likely to be central in leukaemogenesis. The MEF2D/HNRNPUL1 fusion protein was significantly more potent in activating expression than wild-type MEF2D. The rearrangement results in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitivity to histone deacetylase inhibitor treatment (Gu et al., 2016).
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 35354797 | 2022 | Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines. | 119 |
| 35544603 | 2022 | Functional, structural, and molecular characterizations of the leukemogenic driver MEF2D-HNRNPUL1 fusion. | 54 |
| 30171027 | 2019 | Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion. | 43 |
| 38990294 | 2024 | Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements. | 0 |
| 37544723 | 2023 | [Clinical characteristics and outcomes of childhood B-ALL with ZNF384 and MEF2D rearrangements]. | 0 |
| 32504922 | 2020 | Staurosporine and venetoclax induce the caspase-dependent proteolysis of MEF2D-fusion proteins and apoptosis in MEF2D-fusion (+) ALL cells. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 27824051 | 2016 | Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia. | Gu Z et al |
| 27265895 | 2016 | Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. | Lilljebjörn H et al |
| 27428428 | 2016 | Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia. | Liu YF et al |
| 15744350 | 2005 | Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia. | Prima V et al |
| 27019113 | 2016 | Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults. | Yasuda T et al |
| 15182431 | 2004 | Identification of a novel fusion gene in a pre-B acute lymphoblastic leukemia with t(1;19)(q23;p13). | Yuki Y et al |
Summary
Fusion gene
MEF2D/HNRNPUL1
Citation
Tatiana Gindina
t(1;19)(q22;p13.2) MEF2D/HNRNPUL1
Atlas Genet Cytogenet Oncol Haematol. 2019-05-01
Online version: http://atlasgeneticsoncology.org/haematological/1830/t(1
