| Written | 2008-04 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| 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 (FRY-like) |
| Location | 4p11 |
| 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 (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Protein | 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. |
| 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 |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Tue Aug 28 18:17:04 CEST 2018 |
For comments and suggestions or contributions, please contact us