MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)
2005-10-01 Cristina Morerio , Claudio Panarello AffiliationDipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy
Identity
HGNC
LOCATION
10p12.31
IMAGE
LEGEND
AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
FUSION GENES
DNA/RNA
Transcription
5 telomeric --> 3 centromeric direction; 5.5 kb mRNA; coding sequence: 3.1 kb
Proteins
Representation of the AF10 protein modified by Linder B et al. J Mol Biol 2000 and Jones LK et al. Leukemia 2001.
Description
1027 amino acids; 109 KDa; N-term - LAP (leukemia associated protein)/PHD finger - Ext-LAP/PHD (Cys-rich region) - NLS (nuclear localisation signal) - AT-hook - LZ (leucine zipper) - Gln-rich domain - C-term
Expression
mainly in the testis
Localisation
nuclear
Function
transcription factor
Homology
with AF17 and BR140
Implicated in
Entity name
Disease
mainly M4/M5 AML
Cytogenetics
Due to the opposite orientation of AF10 and MLL on their respective chromosome arms, MLL-AF10 gene fusion requires complex rearrangements with three or more breakpoints. An inversion of the 5MLL or 3AF10 is required in order to allow an in-frame MLL-AF10 fusion.
Hybrid gene
5 MLL - 3 AF10; breakpoints are at variable places along AF10
Fusion protein
The AF10 Ext-LAP/PHD is always deleted, as are the MLL PHD fingers. Both retain the C-term LZ domain necessary for malignant transformation.
Disease
One case of pediatric M5 AML
Hybrid gene
5 MLL - 3 AF10 and 5 AF10 - 3 HEAB, a gene at 11q12
Fusion protein
only MLL-AF10 is expressed
Entity name
Disease
Present both in myeloid and non myeloid acute leukemias: in T-cell ALL specific to TCRgd lineage; in myeloid leukemia described in FAB M0-AML, M1-AML, M5-AML, M7-AML.
Prognosis
poor
Cytogenetics
may well be confused with the above t(10;11)(p12;q23)
Hybrid gene
5 CALM - 3 AF10 and 5 AF10 - 3 CALM
In a 5 breakpoint cluster region (nucleotides 424 and 589), AF10 sequences retained the Ext-LAP/PHD domain. The presence of these kind of sequences seems to be necessary for maturation toward the TCRgd lineage, whereas their absence leads to maturation arrest at a more immature stage.
In a 5 breakpoint cluster region (nucleotides 424 and 589), AF10 sequences retained the Ext-LAP/PHD domain. The presence of these kind of sequences seems to be necessary for maturation toward the TCRgd lineage, whereas their absence leads to maturation arrest at a more immature stage.
Fusion protein
both CALM-AF10 and the reciprocal AF10-CALM are expressed. However, the CALM-AF10 contains most of the functional domains present in each of the two proteins.
Breakpoints
Note
the breakpoint in the t(10;11)(p13;q14-21) is more in 5 of AF10
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12676784 | 2003 | CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage. | Asnafi V et al |
| 7542910 | 1995 | Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations. | Bernard OA et al |
| 10637482 | 2000 | Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients. | Bohlander SK et al |
| 7662954 | 1995 | The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. | Chaplin T et al |
| 11135434 | 2001 | Molecular analysis of the genomic inversion and insertion of AF10 into MLL suggests a single-step event. | Chaplin T et al |
| 11986236 | 2002 | The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. | DiMartino JF et al |
| 9616163 | 1998 | MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis. | Dreyling MH et al |
| 11417476 | 2001 | Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia. | Jones LK et al |
| 9365832 | 1997 | Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes. | Kobayashi H et al |
| 9593284 | 1998 | The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants. | Lillington DM et al |
| 9878787 | 1998 | Expression pattern and cellular distribution of the murine homologue of AF10. | Linder B et al |
| 10860745 | 2000 | Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation. | Linder B et al |
| 16111539 | 2005 | MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia. | Morerio C et al |
| 8558942 | 1996 | 11q23 rearrangements in acute leukemia. | Rubnitz JE et al |
| 11896537 | 2002 | Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia. | Van Limbergen H et al |
| 8977038 | 1996 | Chromosome abnormalities in leukaemia: the 11q23 paradigm. | Young BD et al |
Other Information
Locus ID:
NCBI: 8028
MIM: 602409
HGNC: 16063
Ensembl: ENSG00000078403
Variants:
dbSNP: 8028
ClinVar: 8028
TCGA: ENSG00000078403
COSMIC: MLLT10
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33690798 | 2021 | A JAK/STAT-mediated inflammatory signaling cascade drives oncogenesis in AF10-rearranged AML. | 6 |
| 34215314 | 2021 | AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. | 4 |
| 34226546 | 2021 | The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations. | 7 |
| 33690798 | 2021 | A JAK/STAT-mediated inflammatory signaling cascade drives oncogenesis in AF10-rearranged AML. | 6 |
| 34215314 | 2021 | AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. | 4 |
| 34226546 | 2021 | The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations. | 7 |
| 32569758 | 2020 | MLLT10 in benign and malignant hematopoiesis. | 6 |
| 32569758 | 2020 | MLLT10 in benign and malignant hematopoiesis. | 6 |
| 31527241 | 2019 | A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenenic activity. | 11 |
| 31527241 | 2019 | A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenenic activity. | 11 |
| 30102091 | 2018 | MLLT10 promotes tumor migration, invasion, and metastasis in human colorectal cancer. | 2 |
| 30102091 | 2018 | MLLT10 promotes tumor migration, invasion, and metastasis in human colorectal cancer. | 2 |
| 27859216 | 2017 | Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model. | 8 |
| 27859216 | 2017 | Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model. | 8 |
| 26480920 | 2016 | Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat. | 48 |
Citation
Cristina Morerio ; Claudio Panarello
MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)
Atlas Genet Cytogenet Oncol Haematol. 2005-10-01
Online version: http://atlasgeneticsoncology.org/gene/4/chromosome-explorer/meetings/welcome
Historical Card
1997-12-01 MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
