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

Written2008-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1405
 
  t(4;11)(p12;q23) G- banding and FISH - Courtesy Silvia Finkbck, MLL Munich Leukemia Laboratory

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+.

Cytogenetics

Additional anomalies Sole anomaly in 3 cases, accompanied with major karyotypic anomalies in the remaining case: duplication of the der(4), t(1;7)(q10;p10), del(20q), +3, +6, +8, +19, +22.

Genes involved and Proteins

Gene Name FRYL
Location 4p12
Protein 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
Location 11q23
Protein Transcription regulator (yin/yang?), regulates, among others, HOX genes expression. --> hematopoiesis and embryogenesis regulation.

Result of the chromosomal anomaly

Hybrid gene
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.
  
Fusion Protein
Description 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.
  

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.

Bibliography

The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis.
Cong J, Geng W, He B, Liu J, Charlton J, Adler PN.
Development. 2001 Jul;128(14):2793-802.
PMID 11526084
 
Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons.
Emoto K, He Y, Ye B, Grueber WB, Adler PN, Jan LY, Jan YN.
Cell. 2004 Oct 15;119(2):245-56.
PMID 15479641
 
Molecular and cellular mechanisms of dendritic morphogenesis.
Gao FB.
Curr Opin Neurobiol. 2007 Oct;17(5):525-32.
PMID 17933513
 
AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner.
Hayette S, Cornillet-Lefebvre P, Tigaud I, Struski S, Forissier S, Berchet A, Doll D, Gillot L, Brahim W, Delabesse E, Magaud JP, Rimokh R.
Cancer Res. 2005 Aug 1;65(15):6521-5.
PMID 16061630
 
Cellular mechanisms in the development of the Drosophila arista.
He B, Adler PN.
Mech Dev. 2001 Jun;104(1-2):69-78.
PMID 11404081
 
Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases.
He Y, Emoto K, Fang X, Ren N, Tian X, Jan YN, Adler PN.
Mol Biol Cell. 2005 Sep;16(9):4139-52.
PMID 15975907
 
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, Shubinsky G, Moser AM, Gurevitch D, Chatach F, Yermiahu T, Kapelushnik J.
Cancer Genet Cytogenet. 2003 Dec;147(2):110-4.
PMID 14623459
 
Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome.
Robinson BW, Cheung NK, Kolaris CP, Jhanwar SC, Choi JK, Osheroff N, Felix CA.
Blood. 2008 Apr 1;111(7):3802-12.
PMID 18195096
 
Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia.
Sait SN, Claydon MA, Conroy JM, Nowak NJ, Barcos M, Baer MR.
Cancer Genet Cytogenet. 2007 Sep;177(2):143-6.
PMID 17854671
 
Actin filaments and microtubules play different roles during bristle elongation in Drosophila.
Tilney LG, Connelly PS, Vranich KA, Shaw MK, Guild GM.
J Cell Sci. 2000 Apr;113 ( Pt 7):1255-65.
PMID 10704376
 

Citation

This paper should be referenced as such :
Huret, JL
t(4;11)(p12;q23)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):300-301.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0411p12q23ID1405.html


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

Genes FRYL KMT2A

Translocations implicated (Data extracted from papers in the Atlas)

 t(4;11)(p12;q23) KMT2A/FRYL

External links

KMT2A (11q23.3) FRYL (4p11)

Mitelman databaset(4;11)(p12;q23) [Case List]    t(4;11)(p12;q23) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
COSMIC_fusionKMT2A/FRYL KMT2A (11q23.3) FRYL (4p11)   [fusion1968]  
 
Disease databaset(4;11)(p12;q23) KMT2A/FRYL
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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indexed on : Fri Jun 30 11:23:08 CEST 2017


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