t(4;11)(p12;q23) KMT2A/FRYL

2008-04-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

Treatment related diseases

Clinics

Four cases to date:
A 67 year old female patient with acute lymphoblastic leukemia (ALL) following breast adenocarcinoma treatment; latency was 5 years.
A 49 year old female patient with acute myeloid leukemia. The patient have had a non Hogkin lymphoma and a breast adenocarcinoma, 5 years and more before onset of the leukemia.
The third case was that of a 3 year old boy with juvenile myelomonocytic leukemia 17 months after treatment of a pre-B ALL with the typical t(12;21)(p13;q22) (ETV6 / RUNX1).
The fourth case was a 4 year old boy; the t(4;11) was found from bone marrow surveillance, 18 months after diagnosis of a metastatic neuroblastoma ; there was no other evidence of leukemia and the patient carried the t(4;11) and remained healthy for 37 months, before progression to myelodysplasia.

Prognosis

One patient died at 1 month, the 3 others reached complete remission and were alive at 13 months+, 19 months+, and 51 months+.

Genes Involved and Proteins

Gene name
FRYL (FRY-like)
Location
4p11
Protein description
FRYL, also called AF4p12, is the homolog of the Drosophilia melanogaster furry (Fry). Fry maintains the integrity of polarized cell extensions during morphogenesis (Cong et al., 2001; He and Adler, 2001). The morphogenesis of these cell extensions involves the activation of the actin and microtubule cytoskeletons (Tilney et al., 2000). Fry controls various aspects of dendritic outgrowth and branching via the Tricornered (Trc) kinase and Furry (Fry) Trc/Fry signaling pathway; in particular, it may regulate dendritic tiling (non-redundant coverage via dendritic repulsion) and dendritic self-avoidance (Emoto et al., 2004; Gao, 2007).
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Protein description
Transcription regulator (yin/yang?), regulates, among others, HOX genes expression. --> hematopoiesis and embryogenesis regulation.

Result of the Chromosomal Anomaly

Description

In frame fusion between MLL exon 6 and FRYL exon 49 in one case, between MLL exon 8 and FRYL exon 51 in another case.The 2074 or 2156 predicted amino acids of the fusion protein comprise the N-term AT hooks, speckled nuclear localisation signals and repression domains (methyl transferase domain) of MLL, and the leucine zipper domain from FRYL C-term.

Bibliography

Pubmed IDLast YearTitleAuthors
115260842001The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis.Cong J et al
154796412004Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons.Emoto K et al
179335132007Molecular and cellular mechanisms of dendritic morphogenesis.Gao FB et al
160616302005AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner.Hayette S et al
114040812001Cellular mechanisms in the development of the Drosophila arista.He B et al
159759072005Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases.He Y et al
146234592003Conversion of childhood acute lymphocytic leukemia (L2) with a double t(12;21) to juvenile myelomonocytic leukemia with a novel t(4;11)(p12;q23): a cytogenetic, morphologic, and immunophenotypic study.Manor E et al
181950962008Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome.Robinson BW et al
178546712007Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia.Sait SN et al
107043762000Actin filaments and microtubules play different roles during bristle elongation in Drosophila.Tilney LG et al

Summary

Fusion gene

KMT2A/FRYL KMT2A (11q23.3) FRYL (4p11) COF 1968
Atlas Image
t(4;11)(p12;q23) G- banding and FISH - Courtesy Silvia Finkbck, MLL Munich Leukemia Laboratory

Citation

Jean-Loup Huret

t(4;11)(p12;q23) KMT2A/FRYL

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1405/t(4;11)(p12;q23)-kmt2a-fryl

External Links