Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Intrinsically disordered proteins wikipedia , lookup
Protein domain wikipedia , lookup
Protein mass spectrometry wikipedia , lookup
Western blot wikipedia , lookup
Protein purification wikipedia , lookup
Bimolecular fluorescence complementation wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Protein moonlighting wikipedia , lookup
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(6;9)(p23;q34) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0609.html DOI: 10.4267/2042/32108 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Phenotype / cell stem origin Identity M2, M4 ANLL, often preceded by MDS; M1 ANLL or RAEB at times; May be secondary to toxic exposure; A primitive myeloid progenitor is likely to be involved. Epidemiology 1% of ANLL; Found at any age, but median age (25-30 yrs) is less than usual in ANLL; Rare in the elderly; Sex ratio: 1M/1F; Blood data: marked basophilia (> 1% of nucleated cells) in one third to half of the patients. Cytology TdT +; Auer rods. Prognosis Remission difficult to obtain; CR in only half cases; median survival around 1 yr. Cytogenetics Cytogenetics, morphological May be over loocked. Additional anomalies Most often none (80%); recurrent, although rare, additional anomalies are: +8, +13, +21. Variants Three way complex t(6;9;Var) exist. Genes involved and Proteins t(6;9)(p23;q34) G-banding - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center (top and middle top), Jean-Luc Lai (middle below), and Roland Berger (below). DEK Location: 6p23 Protein Clinics and pathology Contains acidic domains and a nuclear localisation signal; DNA binding protein; transcriptional regulation and signal transduction. Disease ANLL and/or MDS. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 29 t(6;9)(p23;q34) Huret JL The translocation t(6;9)(p23;q34) results in the formation of a chimeric fusion gene: DEK (6q23) and CAN (9q34). CAN is a putative oncogene which may be activated by fusion of its 3' end to other genes than DEK. One such recently reported gene is called SET and leads to expression of a SET/CAN fusion RNA. The t(6;9)(p21-22;q34) may be seen in either AML M2 or less frequently in M4 or MDS and acute myelofibrosis often in association with excess basophils. The t(6;9) is reported mostly in young adults. The prognosis of patients carrying the t(6;9) is unfavorable - Courtesy Georges Flandrin, CD-ROM AML/MDS G.Flandrin/ICG. TRIBVN. CAN Detection protocol Location: 9q34 RNA-PCR. Protein Fusion protein Contains dimerization domains → forms homodimers; nuclear membrane localisation; associated with the nuclear pore complex. Description Results of the chromosomal anomaly Expression localisation 165 kDa; N-term with almost the entire DEK protein fused to the C-terminal two-thirds of the CAN protein. Nuclear localisation. References Hybrid gene Pearson MG, Vardiman JW, Le Beau MM, Rowley JD, Schwartz S, Kerman SL, Cohen MM, Fleischman EW, Prigogina EL. Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL. Am J Hematol 1985 Apr;18(4):393-403. Description 5' DEK - 3' CAN on der(6); Head to tail DEK/CAN fusion gene (SET/CAN exceptional); breakpoint clusters in a single intron of 8 kb (ICB9: 'intron containing breakpoint 9') in CAN, and in a single intron (of 12 kb) as well (ICB6) in DEK. von Lindern M, Poustka A, Lerach H, Grosveld G. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. Mol Cell Biol 1990 Aug;10(8):4016-26. Transcript Soekarman D, von Lindern M, van der Plas DC, Selleri L, Bartram CR, Martiat P, Culligan D, Padua RA, Hasper-Voogt 5.5 kb RNA; no CAN-DEK reciprocal transcript on chromosome 9. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 30 t(6;9)(p23;q34) Huret JL KP, Hagemeijer A, et al. Dek-can rearrangement in translocation (6;9)(p23;q34). Leukemia 1992 Jun;6(6):489-94. Fornerod M, Boer J, van Baal S, Morreau H, Grosveld G. Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 1996 Oct 17;13(8):1801-8. von Lindern M, Fornerod M, Soekarman N, van Baal S, Jaeglé M, Hagemeijer A, Bootsma D, Grosveld G. Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. Baillieres Clin Haematol 1992 Oct;5(4):857-79. (Review). This article should be referenced as such: Huret JL. t(6;9)(p23;q34). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):29-31. Lillington DM, MacCallum PK, Lister TA, Gibbons B. Translocation t(6;9)(p23;q34) in acute myeloid leukemia without myelodysplasia or basophilia: two cases and a review of the literature. Leukemia 1993 Apr;7(4):527-31. (Review). Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 31