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NOVEL GENETIC ABNORMALITY RELATED TO ACUTE LYMPHOBLASTIC LEUKEMIA, AND USES THEREOF NEW

外国特許コード F170009136
整理番号 (S2016-0212-N0)
掲載日 2017年7月28日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2016JP088570
国際公開番号 WO 2017111129
国際出願日 平成28年12月22日(2016.12.22)
国際公開日 平成29年6月29日(2017.6.29)
優先権データ
  • 特願2015-255179 (2015.12.25) JP
発明の名称 (英語) NOVEL GENETIC ABNORMALITY RELATED TO ACUTE LYMPHOBLASTIC LEUKEMIA, AND USES THEREOF NEW
発明の概要(英語) The present invention addresses the problem of discovering a novel genetic abnormality, which is useful for the determination of treatment strategies or prognostic prediction of acute lymphoblastic leukemia, and contributing to the improvement of treatment outcomes. A genetic abnormality characterized by the formation of a fusion gene comprising the MEF2D gene and the BCL9 gene has been discovered from recurrent childhood acute lymphoblastic leukemia patients. This genetic abnormality will serve as a new indicator when determining treatment strategies.
特許請求の範囲(英語) [claim1]
1. The step (1)-(3) below is included, inspection method of the acutely lymph characteristic leukemia:
(1) the step which prepares the inspection body which includes the leukemia cell which is isolated from the acutely lymph characteristic leukemia patient;
(2) in the aforementioned inspection body, the fused gene or the said fused gene of the MEF2D gene and the BCL9 gene the cord/code the step which detects the presence of the fusion protein which is done;
(3) when the aforementioned fused gene or the aforementioned fusion protein is detected as the convalescence defectiveness or remedy difficulty the step which is decided.
[claim2]
2. With the MEF2D gene the cut vertex exists in tron 6 or 7, the aforementioned fused gene is formed with the BCL9 gene Exxon 8 or by the chromosome inversion where the cut vertex exists in tron 9, in claim 1 inspection method of statement.
[claim3]
3. In step detection of the aforementioned fusion protein (2) detection of the aforementioned fused gene, is done RT-PCR method and PCR method, PCR-RFLP, PCR-SSCP method, RNA sequence analysis and target sequence analysis, by each detection method which is selected from FISH method, and the group which consists of all the genome analyses in step (2) is done by immunology measurement method, in claim 1 or 2 inspection method of statement.
[claim4]
4. The aforementioned acutely lymph characteristic leukemia patient is the child, either of the claim 1-3 in one section inspection method of statement.
[claim5]
5. Step below (4) or (4 ') furthermore it includes, either of the claim 1-4 in one section inspection method of statement:
(4) the aforementioned step (3) on the basis of decision, the step which the risk group to which the aforementioned acutely lymph characteristic leukemia patient belongs specifies, it decides or modifies remedy policy;
(4 ') the aforementioned step (3) on the basis of the result of inspection of decision and other things, the step which the risk group to which the aforementioned acutely lymph characteristic leukemia patient belongs specifies, it decides or modifies remedy policy.
[claim6]
6. The aforementioned risk group is the high risk group, in claim 5 inspection method of statement.
[claim7]
7. The aforementioned step (4) or (4 ') with after modifying, remedy policy, includes the medical therapy which is strengthened than before the modifying, in claim 5 or 6 inspection method of statement.
[claim8]
8. The aforementioned step (4) or (4 ') with decided or after modifying, remedy policy, the histone deacetylation conversion enzyme inhibiter and/or includes the disposal which is due to the dosage of the puroteasomu inhibiter, in claim 5 or 6 inspection method of statement.
[claim9]
9. The aforementioned histone deacetylation conversion enzyme inhibiter is the histone deacetylation conversion enzyme 9 inhibiter, in claim 8 inspection method of statement.
[claim10]
10. The aforementioned step (4) or (4 ') with decided or after modifying, remedy policy, includes the adaptation of hemotopoiesis trunk cell transplantation, in claim 5 or 6 inspection method of statement.
[claim11]
11. The aforementioned hemotopoiesis trunk cell transplantation is executed in 1st Hiroshi solution period, in claim 10 inspection method of statement.
[claim12]
12. In one section it decided with inspection method of statement or either of the claim 5-11 after modifying, following to remedy policy, the fact that the aforementioned acutely lymph characteristic leukemia patient is dealt with is included, remedy method of the acutely lymph characteristic leukemia.
[claim13]
13. The medicine in order to remedy the acutely lymph characteristic leukemia patient who the histone deacetylation conversion enzyme inhibiter and/or includes the puroteasomu inhibiter, is characterized with formation of the fused gene of the MEF2D gene and the BCL9 gene.
[claim14]
14. The aforementioned histone deacetylation conversion enzyme inhibiter is the histone deacetylation conversion enzyme 9 inhibiter, in claim 13 the medicine of statement.
[claim15]
15. The histone deacetylation conversion enzyme inhibiter and/or the medicine which includes the puroteasomu inhibiter in regard to remedy the effective quantity the fact that it prescribes is included vis-a-vis the acutely lymph characteristic leukemia patient who is characterized with formation of the fused gene of the MEF2D gene and the BCL9 gene, remedy method of the acutely lymph characteristic leukemia.
[claim16]
16. The aforementioned histone deacetylation conversion enzyme inhibiter is the histone deacetylation conversion enzyme 9 inhibiter, in claim 15 remedy method of statement.
[claim17]
17. With the MEF2D gene the cut vertex exists in tron, 6 or 7 is formed with the BCL9 gene Exxon 8 or by the chromosome inversion where the cut vertex exists in tron 9, in order to be able to expand complimentary DNA uniquely in mRNA which is the copying product of the fused gene of the MEF2D gene and the BCL9 gene, the primer set which consists of the forward primer and the reverse primer which are designed.
[claim18]
18. In order with the MEF2D gene for the cut vertex to exist in tron, 6 or 7 to be formed with the BCL9 gene Exxon 8 or by the chromosome inversion where the cut vertex exists in tron 9, to be able to expand the fused gene of the MEF2D gene and the BCL9 gene uniquely the primer set which consists of the forward primer and the reverse primer which are designed.
[claim19]
19. The kit for the detection of genetics abnormality which in claim includes the primer set of statement 17 or 18, is characterized with formation of the fused gene of the MEF2D gene and the BCL9 gene.
[claim20]
20. Primer set below is included as the aforementioned primer set, in claim 19 the kit for detection of statement:
Being one part of the territory of the Exxon 1-6 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more
[claim21]
21. (A1) below the - (a3) one or more in is included as the aforementioned primer set, in claim 19 the kit for detection of statement:
(A1) Being one part of the territory of the Exxon 3-4 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more;
(A2) Being one part of the territory of the Exxon 5-6 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more;
(A3) Being one part of the territory of Exxon 6 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more.
[claim22]
22. (B1) below and/or (b2) it includes as the aforementioned primer set, in claim 19 the kit for detection of statement:
(B1) Being one part of the territory of Exxon 2 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more;
(B2) Being one part of the territory of Exxon 5 of the MEF2D gene, being one part of the territory of Exxon 10 of the forward primer and the BCL9 gene which consist of complimentary arrangement in the part which consists of 13 bases or more the primer set which consists of the reverse primer which consists of complimentary arrangement in the part which consists of 13 bases or more.
[claim23]
23. Screening method of the substance which is effective to the remedy of the acutely lymph characteristic leukemia patient who includes the step (i)-(iii) below, is characterized with formation of the fused gene of the MEF2D gene and the BCL9 gene:
(i) The step which prepares the cell which reveals the fused gene of the MEF2D gene and the BCL9 gene;
(ii) Under existing of the test substance, the step which cultures the aforementioned cell;
(iii) The step which measures the number of existences of the cell, decides the effectiveness of the aforementioned test substance.
[claim24]
24. Fused gene of MEF2D gene and BCL9 gene.
[claim25]
25. With the MEF2D gene the cut vertex exists in tron, 6 or 7 occurs with the BCL9 gene Exxon 8 or with the chromosome inversion where the cut vertex exists in tron 9, in claim 24 the fused gene of statement.
[claim26]
26. The Exxon 1-6 of the MEF2D gene and Exxon 10 of the BCL9 gene or the part of that is included, in claim 25 the fused gene of statement.
[claim27]
27. Arrangement of arrangement of arrangement number 11 and arrangement number 12 is included, in claim 26 the fused gene of statement.
[claim28]
28. Either of the claim 24-27 in one section the fused gene of statement the cord/code the fusion protein which is done.
[claim29]
29. Arrangement of arrangement of arrangement number 13 and arrangement number 14 is included, in claim 28 the fusion protein of statement.
[claim30]
30. Either of the claim 24-27 in mRNA which is the copying product of the fused gene of statement in one section complimentary DNA.
[claim31]
31. Arrangement of arrangement of arrangement number 15 and arrangement number 16 is included, in claim 30 DNA of statement.
[claim32]
32. The fused gene of the MEF2D gene and the BCL9 gene the cord/code the antibody which recognizes the fusion protein which is done.
[claim33]
33. The aforementioned fusion protein, is the fusion protein which is defined in claim 28 or 29, in claim 32 the antibody of statement.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NAGOYA UNIVERSITY
  • 発明者(英語)
  • OKUNO YUSUKE
  • KOJIMA SEIJI
  • SUZUKI KYOGO
  • KAWASHIMA NOZOMU
  • SEKIYA YUKO
国際特許分類(IPC)
指定国 (WO2017111129)
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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