XL t(10;11) MLLT10/KMT2A DF consists of an orange-labeled probe hybridizing to the MLLT10 gene region at 10p12.3 and a green-labeled probe hybridizing to the KMT2A gene region at 11q23.3.

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. MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor), previously known as AF10, is one of the most frequent fusion partners of KMT2A across all acute leukemia cases. KMT2A-MLLT10 fusions result from multiple breakpoints in both gene loci. The subsequent chromosomal rearrangements include reciprocal translocations, insertions, inversions, deletions and duplications. MLLT10 is a cofactor of the histone H3K79 methyltransferase DOT1L and mediates the interaction of AFF1, MLLT1 and MLLT3 with DOT1L. The consequence of the presence of KMT2A-AFF1, AFF1-KMT2A, KMT2A-MLLT3, KMT2A-MLLT1, and KMT2A-MLLT10 fusions is an increased and extended H3K79 methylation signature that is a requirement for the maintenance of RNA transcription. DOT1L inhibitors are promising candidates for clinical treatment which are currently being evaluated.

Clinical Applications

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

XL t(10;11) MLLT10/KMT2A DF hybridized to bone marrow cells, two aberrant cells are shown. An insertion of portions of the green signal into the orange signal has occured generating a pattern of 2 green, one orange and one green-orange colocalization/fusion signal.

• De Braekeleer et al (2011) Mol Oncol 5:555-563
• Meyer et al (2013) Leukemia 27:2165- 2176
• Peterson et al (2019) Genes Chromosomes Cancer 58:567-577

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• 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.