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t(10;11)(q22;q23) KMT2A::TET1

Written2014-06Antoine Ittel
Laboratoire de Cytogenetique hematologique, CHU Hautepierre, Strasbourg, France
This article is an update of :
2008-02Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

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ICD-Morpho 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1410

Clinics and Pathology

Disease Acute myeloid leukemia (AML), B-cell precursor acute lymphoblastic leukemia (ALL), T-cell lymphoblastic lymphoma
Phenotype / cell stem origin Described in subtypes AML-M2, -M4 and -M5. Cell lineage dysplasia may be associated. Described also in 2 B-ALL and one case of T-cell lymphoblastic lymphoma with a subsequent transformation to AML.
Epidemiology Described in 14 cases in the literature, mainly adults and 2 children (8 men, 5 women, 1 unknown) median age of 39 years (range 1 month to 67 years).
Frequency estimated at 0.3 % of MLL-rearranged acute leukemia cases (5 out 1590) (Lee et al., 2013).
Prognosis Undetermined, possibly intermediate. On the 8 of 14 patients with available clinical outcomes, 7 had a complete remission. 6 patients died at an average of 16 months after initial diagnosis.


Cytogenetics Morphological Easy to detect, evident 10q- and 11q+ derivatives.
  A. t(10;11)(q22;q23) in GTG banding. B. The same with RHG banding.
Cytogenetics Molecular Commercial dual color MLL/KMT2A FISH probes are splitted by the translocation. 10q22 breakpoint may be detected with RP11-119F7 BAC probe or using RP11-9E13 and RP11-314J18 BACs (separation of the two BACs with the t(10;11)(q22;q23)).
  A. FISH on metaphase (inverted DAPI) using RP11-9E13 and RP11-314J18 BACs showing the separation of the two probes in the t(10;11)(q22;q23). B. Focus on chromosomes 10 and 11 and derivative chromosomes (inverted DAPI) from the t(10;11) with the same BACs.
Additional anomalies 5/11 caryotypes available have the t(10;11) as sole chromosomal abnormality. 4/11 have one more chromosomal abnormality (+21, del(6)p(21), del(5)(q15), add(13)(p11) or der(6)t(6;?9)(p22;?q21) in 2 different clones with the t(10;11)); one case was hyperdiploid with 51 chromosomes; one case had complex caryotype.

Genes involved and Proteins

Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Note KMT2A is also called MLL (mixed-lineage leukemia or myeloid-lymphoid leukaemia), ALL-1 or HRX.
Dna / Rna 36 exons, multiple transcripts 13-15 kb.
Protein 430 kDA, contains two DNA binding motifs (a AT hook and a CXXC domain), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor involved in maintenance of Hox gene expression during embryogenesis and during the process of haematopoietic progenitors expansion and differentiation.
Gene NameTET1 (tet methylcytosine dioxygenase 1)
Location 10q21.3
Note TET1 is also called LCX (leukemia-associated protein with a CXXC domain) or CXXC6 (CXXC finger 6).
Dna / Rna 8497 bp representing the whole coding sequence. Contains 12 exons. Contains 3 bipartite nuclear localization sites, 1 alpha helice coiled-coil region and 1 cysteine rich domain with high level homology with a CXXC DNA binding site.
Protein Predicted size of 2136 amino acids, expression restricted to some fetal tissues, mainly lung, heart and brain; not expressed in hematopoietic tissues, except in spleen; unknown function.
TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Key role in active DNA demethylation. TET1 and TET2: key enzymes responsible for the presence of 5hmC in mouse embryonic stem cells (ESCs). TET1: regulates the lineage differentiation potential of ESCs. TET1 interacts physically with NANOG, synergistically enhancing the efficiency of NANOG in somatic cell reprogramming. NANOG/TET1 co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and may deposit 5hmC to target genes before the establishment of pluripotency. Taken together, these observations suggest a possible mechanism for the lineage switch observed in one of the 14 cases. (Ittel et al., 2013).
TET1 significantly up-regulated in MLL-rearranged leukemia. TET1: direct target gene of MLL-fusion proteins. MLL fusions bind to the promoter region of TET1 and promote its expression directly in both human and mouse hematopoietic stem/progenitor cells, cumulating in a global increase of 5hmC. Briefly, MLL-fusion proteins bind directly to the Tet1 locus. Consequently this promote its expression and the increased expression of Tet1 (and the corresponding global increase of 5hmC) cooperates with MLL fusions in orchestrating the transcriptional activation of their cotargets. The main critical oncogenic cotargets described are HOXA9, MEIS1 and PBX3. The Hoxa9/Meis1/Pbx3 signaling cascade promotes cell proliferation and inhibits apoptosis/cell differentiation, thereby leading to cell transformation and leukemogenesis. (Huang et al., 2013).

Result of the chromosomal anomaly

Hybrid gene
Description Transcripts from the 5' MLL-LCX 3' fusion gene on der(11) are expressed; transcripts from the 5' LCX-MLL 3' counterpart are not detected.
Breakpoints in the MLL gene are located between intron 6 and exon 11.
All genomic breakpoints within the TET1 gene were identified in an approximately 17 kb genomic region flanked by TET1 exons 8 and 12. Most characterized breakpoints (5 of 7 cases) were mapped to intron 8.
Fusion Protein
Description Predicted molecular weight of 204.4 kDa.
Oncogenesis Unknown; the alpha helice coiled-coil region retained at the COOH extremity might be involved in the leukemogenesis.

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Involvement of MLL gene in a t(10;11)(q22;q23) and a t(8;11)(q24;q23) identified by fluorescence in situ hybridization.
Aventin A, La Starza R, Martinez C, Wlodarska I, Boogaerts M, Van den Berghe H, Mecucci C.
Cancer Genet Cytogenet. 1999 Jan 1;108(1):48-52.
PMID 9973924
TET1 plays an essential oncogenic role in MLL-rearranged leukemia.
Huang H, Jiang X, Li Z, Li Y, Song CX, He C, Sun M, Chen P, Gurbuxani S, Wang J, Hong GM, Elkahloun AG, Arnovitz S, Wang J, Szulwach K, Lin L, Street C, Wunderlich M, Dawlaty M, Neilly MB, Jaenisch R, Yang FC, Mulloy JC, Jin P, Liu PP, Rowley JD, Xu M, He C, Chen J.
Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11994-9. doi: 10.1073/pnas.1310656110. Epub 2013 Jul 1.
PMID 23818607
First description of the t(10;11)(q22;q23)/MLL-TET1 translocation in a T-cell lymphoblastic lymphoma, with subsequent lineage switch to acute myelomonocytic myeloid leukemia.
Ittel A, Jeandidier E, Helias C, Perrusson N, Humbrecht C, Lioure B, Mazurier I, Mayeur-Rousse C, Lavaux A, Thiebault S, Lerintiu F, Gervais C, Mauvieux L.
Haematologica. 2013 Dec;98(12):e166-8. doi: 10.3324/haematol.2013.096750.
PMID 24323992
Identification and characterization of human CXXC10 gene in silico.
Katoh M, Katoh M.
Int J Oncol. 2004 Oct;25(4):1193-9.
PMID 15375572
Genomic breakpoints and clinical features of MLL-TET1 rearrangement in acute leukemias.
Lee SG, Cho SY, Kim MJ, Oh SH, Cho EH, Lee S, Baek EJ, Choi JH, Bohlander SK, Lode L, Richebourg S, Yoon HJ, Marschalek R, Meyer C, Park TS.
Haematologica. 2013 Apr;98(4):e55-7. doi: 10.3324/haematol.2012.076323. Epub 2012 Oct 25.
PMID 23100278
TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23).
Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR.
Leukemia. 2003 Mar;17(3):637-41.
PMID 12646957
LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).
Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y.
Cancer Res. 2002 Jul 15;62(14):4075-80.
PMID 12124344


This paper should be referenced as such :
A Ittel
t(10;11)(q22;q23) KMT2A/TET1
Atlas Genet Cytogenet Oncol Haematol. 2015;19(2):141-144.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Viguié, F. t(10;11)(q22;q23). Atlas Genet Cytogenet Oncol Haematol. 2009;13(2):137-138.

Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes KMT2A TET2

Translocations implicated (Data extracted from papers in the Atlas)

 t(10;11)(q22;q23) KMT2A/TET1

External links

KMT2A (11q23.3) TET1 (10q21.3)

Mitelman databaset(10;11)(q22;q23)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9807/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9813/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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