t(9;11)(p21;q23) KMT2A/MLLT3

2016-03-01   Jeroen Knijnenburg , Jeroen Knijnenburg 

1.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. b.beverloo@erasmusmc.nl
2.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Abstract

Review on t(9;11)(p21;q23), with data on clinics, and the genes involved.

Clinics and Pathology

Disease

Acute myeloid leukemia (AML).

Phenotype stem cell origin

Most often found in acute monocytic and myelomonocytic leukaemias, although occasionally also seen in AML with or without maturation (WHO 2008).
M5 most often (especially M5a, M4); both found in de novo and therapy related AML with antitopoisomerase II drugs (epipodophyllotoxins, anthracyclins, actinomycin D).
Immunophenotype typically shows positivity for CD11, CD13, CD15 and CD33, but less often shows positivity for CD14, CD34 and lymphoid markers.

Epidemiology

May occur at any age, but is more common in children, being present in 5-12% of paediatric and 1-2% of adult AML, and equally common in males and females.

Clinics

Organomegaly, frequent central nervous system (CNS) involvement, especially in de novo cases; no preceding myelodysplastic phase, unlike classic therapy related AML with chromosome 5 and/or 7 involvement, short interval from initial drug therapy (may even be of 1-2 yrs). Patients may present with disseminated intravascular coagulation and may have tissue infiltration.

Cytology

Absence of trilineage dysplasia, unlike classic therapy related AML.

Prognosis

Survival is described as poor to intermediate, being superior to AML with other KMT2A translocations.

Cytogenetics

Cytogenetics morphological

May easily be overlooked. Previously described as t(9;11)(p22;q23) based on band estimation, but nowadays it is known that MLLT3 is located in 9p21.3 based on molecular positioning.

Cytogenetics molecular

FISH or RT-PCR is indicated in cases with poor chromosome morphology or in cases where the translocation is expected in cases based on morphology, immunophenotype or clinical presentation.

Additional anomalies

None in 70% of cases, +8 in 20%, less frequently: additional trisomies of chromosome 6, 19 or 21.

Variants

Complex 3 way translocations t(9;11;Var) involving a (variable) third chromosome and insertions have been described, and showed that der(11) is the crucial on

Genes Involved and Proteins

Gene name
MLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3)
Location
9p21.3
Protein description
Contains a nuclear targeting sequence; transcriptional activator; nuclear localisation.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Protein description
Contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation.

Result of the Chromosomal Anomaly

Description

5 KMT2A- 3 MLLT3; variable breakpoints.N-term -- AT hook and DNA methyltransferase from KMT2A (1444 amino acids) fused to the 192 C-term amino acids from MLLT3 (as breakpoints are variable, this is only an exemple); 180 kDa.

Expression localisation

Nuclear localisation.

Bibliography

No bibliography items were found for this article.

Summary

Fusion gene

KMT2A/MLLT3 KMT2A (11q23.3) MLLT3 (9p21.3) TIC
Atlas Image
t(9;11)(p21;q23) KMT2A/MLLT3 G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top 2 rows), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (rows 3 to 6); Courtesy  Adriana Zamecnikova (rows 7 and 8); R-banding (right): top: - Courtesy Pascale Cornillet-Lefebvre and Stu00e9phanie Struski, center top: t(9;11)+der(9)t(9;11) - Courtesy Christiane Charrin; bottom 2: - Courtesy Hossein Mossafa. FISH: u201cRedu201d chromosomes - Courtesy Pascale Cornillet-Lefebvre and Stu00e9phanie Struski. The probe is MLL; one signal is on the normal 11, one signal on the der(11), and one signal (arrow) on the der(9); pale blue chromosomes - Courtesy Hossein Mossafa (AN: abnormal). (); bottom 3: Hybridization with Kreatech KMT2A/MLLT3 t(9;11) fusion probe (Leica Biosystems, US) showing hybridization on normal (A) and on metaphases with t(9;11) (B,C). - Courtesy  Adriana Zamecnikova.

Citation

Jeroen Knijnenburg ; Jeroen Knijnenburg

t(9;11)(p21;q23) KMT2A/MLLT3

Atlas Genet Cytogenet Oncol Haematol. 2016-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1001/t(9;11)(p21;q23)

Historical Card

1997-12-01 t(9;11)(p21;q23) KMT2A/MLLT3 by  Jean-Loup Huret,Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

External Links