XL t(11;19) KMT2A/ELL DF consists of a green-labeled probe hybridizing to the KMT2A gene region at 11q23.3 and an orange-labeled probe hybridizing to the ELL gene region at 19p13.1.

Probe maps are created in accordance with the intended purpose of the product. Solid colored bars do not necessarily indicate that the probe fully covers the indicated genomic region. Therefore, caution is advised when interpreting results generated through off-label use. Probe map details based on UCSC Genome Browser GRCh37/hg19. Map components not to scale. Further information is available on request.

Chromosomal rearrangements of the KMT2A (lysine methyltransferase 2A) gene, formerly MLL (mixed lineage leukemia), are associated with various hematological disorders. Most patients suffer from acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), while only a minority develops mixed lineage leukemia (MLL). Several chromosomal aberrations involving the KMT2A gene have been identified. However, the majority of leukemias result from translocations leading to KMT2A fusions. More than 90 KMT2A translocation partner genes fused to the 5´- KMT2A portion have been identified. The most common translocation partners in KMT2A associated leukemia are AFF1, MLLT3, MLLT1, MLLT10, ELL and AFDN, described here in the order of their frequency. Fusions between KMT2A and ELL (elongation factor for RNA polymerase II), caused by translocations of the type t(11;19)(q23;p13.1), belong to the most common KMT2A fusion genes in AML. Approximately 11% of AML patients carrying KMT2A rearrangements are characterized by the KMT2A-ELL fusion gene. The breakpoints within the KMT2A gene resulting in KMT2A-ELL fusions are found in intron 9 in the case of patients younger than one year and in intron 11 in the case of patients older than one year. This breakpoint distribution is unique among all KMT2A fusions. The outcome of patients with breakpoints in KMT2A intron 11 is worse compared to patients with upstream breakpoints. ELL is a component of the super elongation complex (SEC). Chimeric KMT2A-ELL fusion proteins have the ability to recruit SEC resulting in aberrant gene expression.

Clinical Applications

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)

XL t(11;19) KMT2A/ELL DF hybridized to bone marrow cells, two aberrant cells are shown. Translocations are typically observed as one orange and one green signal clearly separated and two orange-green colocalization/fusion signals.

• De Braekeleer et al (2011) Mol Oncol 5:555-563
• Meyer et al (2017) Leukemia 32:273–284
• Chan and Chen (2019) Front Cell Dev:doi:10.3389/fcell.2019.00081

• Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.
• A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature.
• Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.
• Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.
• Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.
• Fluorescence in situ hybridisation assays designed for del(7q) detection uncover more complex rearrangements in myeloid leukaemia cell lines
• Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation.
• A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasiaresulting in a fusion of IGL and CCND1: case report.
• Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions.