t(4;11)(p12;q23) KMT2A/FRYL
2008-04-01 Jean-Loup Huret Affiliation1.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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11526084 | 2001 | The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis. | Cong J et al |
| 15479641 | 2004 | Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons. | Emoto K et al |
| 17933513 | 2007 | Molecular and cellular mechanisms of dendritic morphogenesis. | Gao FB et al |
| 16061630 | 2005 | AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner. | Hayette S et al |
| 11404081 | 2001 | Cellular mechanisms in the development of the Drosophila arista. | He B et al |
| 15975907 | 2005 | Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases. | He Y et al |
| 14623459 | 2003 | Conversion 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 |
| 18195096 | 2008 | Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome. | Robinson BW et al |
| 17854671 | 2007 | Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia. | Sait SN et al |
| 10704376 | 2000 | Actin 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
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
