MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)

2005-10-01 Cristina Morerio , Claudio Panarello Affiliation

Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy

Identity

HGNC

MLLT10

LOCATION

10p12.31

IMAGE

LEGEND

AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LOCUSID

8028

FUSION GENES

Show Gene Fusions

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

t(10;11)(p12;q23)/AML -->KMT2A-MLLT10

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.

Entity name

inv ins(10;11)(p12;q23q12)/AML -->KMT2A - MLLT10

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

t(10;11)(p13;q14-21)-->CALM-MLLT10 and/or AF10-CALM

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.

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

Gene ID	Transcript ID	Uniprot
ENSG00000078403	ENST00000307729	P55197
ENSG00000078403	ENST00000377059	P55197
ENSG00000078403	ENST00000377072	P55197
ENSG00000078403	ENST00000377091	P55197
ENSG00000078403	ENST00000377100	P55197
ENSG00000078403	ENST00000420525	H0Y5P4
ENSG00000078403	ENST00000430455	H0Y5C4
ENSG00000078403	ENST00000438473	Q5JT35
ENSG00000078403	ENST00000462999	A0A494C093
ENSG00000078403	ENST00000495130	A0A494C1P9
ENSG00000078403	ENST00000621220	P55197
ENSG00000078403	ENST00000631589	P55197
ENSG00000078403	ENST00000650772	A0A494C0R2
ENSG00000078403	ENST00000650893	A0A494C1P9
ENSG00000078403	ENST00000651097	A0A494C038
ENSG00000078403	ENST00000651298	A0A494C1P9
ENSG00000078403	ENST00000652497	P55197

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/mllt10-(myeloid-lymphoid-or-mixed-lineage-leukemia-(trithorax-homolog-drosophila);-translocated-to-10)

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