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ADULT T-CELL LEUKEMIA-LYMPHOMA DETECTION METHOD

Foreign code F200010236
File No. (S2019-0201-N0)
Posted date Oct 29, 2020
Country WIPO
International application number 2020JP008206
International publication number WO2020179646
Date of international filing Feb 28, 2020
Date of international publication Sep 10, 2020
Priority data
  • P2019-037246 (Mar 1, 2019) JP
Title ADULT T-CELL LEUKEMIA-LYMPHOMA DETECTION METHOD
Abstract An adult T-cell leukemia-lymphoma (ATL) detection method is provided which involves determining the presence or absence in a target biological sample of DNA methylation of at least one gene selected from the group consisting of SERPINB6, NELL2, THEMIS, ZSCAN18, LAIR1, CD7, RNF130, ZIK1, LYPD3, TMEM45B, POMC, FHIT, MDS2, HOOK1, SORCS3, C2orf40, ZNF662, SPG20, ZNF717, LZTFL1, KLHL34 and BCL9, wherein DNA methylation of at least one of the aforementioned genes indicates that the subject has developed or is at risk of developing ATL. By this means, a new detection method of adult T cell leukemia-lymphoma (ATL) is provided.
Outline of related art and contending technology BACKGROUND ART
Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell tumor caused by infection of T cells with retrovirus Human T-cell Lymphotropic Virus type-1 (HTLV-1). HTLV-1 is mainly infected by lactation, sex, transfusion, and the like, and HTLV-1 infants are localized in Japan, Calib sea coastal countries, central Africa, South America, and the like, and are estimated to be 500 million persons and ~ 2,000 million persons as a whole. HTLV-1 infectants in Japan are estimated to be 110 million, and (non-patent documents 1) and 40 ~ 50 % are unevenly distributed in Kyushu and okinawa district, but in recent years, HTLV-1 infectants in metropolitan areas such as Osaka, Tokyo and Aichi tend to increase.
HTLV-1-infected T cells undergo a multistage carcinogenesis process, which acquires clonic proliferation ability while accumulating genetic mutations and epigenetic abnormalities. Therefore, (Non-Patent Document 1) is characterized in that the period from infection to onset of ATL is very long, and as a result, there are many ATL onset persons in elderly carriers. On the other hand, most of HTLV-1 infected patients end their life as asymptomatic infected patients, but 3 ~ 5 % of infected patients develop ATL, and their clinical pathologies are classified into sod, chronic, acute and lymphoma types. Acute and lymphoma types and some chronic types having poor prognosis factors have high malignancy and very poor prognosis. On the other hand, the chronic type which does not have the poor prognosis factor is considered to be low grade ATL which follows relatively slow progress, and direct therapeutic intervention is not basically performed. However, (Non-Patent Document 2), in which approximately half of the low grade ATL patients have acute conversion over the course and the long-term prognosis thereof is poor. Therefore, it is desired to develop effective methods for preventing and treating ATL onset.
Scope of claims (In Japanese)[請求項1]
 対象の生体サンプルにおいて、SERPINB6、NELL2、THEMIS、ZSCAN18、LAIR1、CD7、RNF130、ZIK1、LYPD3、TMEM45B、POMC、FHIT、MDS2、HOOK1、SORCS3、C2orf40、ZNF662、SPG20、ZNF717、LZTFL1、KLHL34及びBCL9遺伝子からなる群から選択される少なくとも1種の遺伝子のDNAメチル化の有無を測定することを含み、前記少なくとも1種の遺伝子がDNAメチル化されていることが、対象が成人T細胞白血病/リンパ腫(ATL)を発症している又は発症する恐れがあることを示す、ATLの検出方法。

[請求項2]
 前記少なくとも1つの遺伝子のDNAメチル化を、バイサルファイトシークエンス法によって測定する、請求項1に記載の方法。

[請求項3]
 前記少なくとも1種の遺伝子が、
(1)SERPINB6、NELL2、THEMIS、ZSCAN18、LAIR1、CD7、RNF130、ZIK1、LYPD3、TMEM45B、POMC、FHIT、MDS2、HOOK1、SORCS3、C2orf40、ZNF662、SPG20、ZNF717、LZTFL1、KLHL34及びBCL9遺伝子を含む組み合わせ、
(2)LYPD3、THEMIS、NELL2、及びC2orf40遺伝子を含む組み合わせ、
(3)LYPD3、THEMIS、NELL2、C2orf40、HOOK1、FHIT、CD7、MDS2、及びLAIR1遺伝子を含む組み合わせ、
(4)LYPD3、THEMIS、NELL2、C2orf40、HOOK1、FHIT、CD7、MDS2、LAIR1、RNF130、POMC、及びBCL9遺伝子を含む組み合わせ、または
(5)LYPD3、THEMIS、NELL2、C2orf40、HOOK1、FHIT、CD7、MDS2、LAIR1、RNF130、POMC、BCL9、LZTFL1、ZIK1、及びTMEM45B遺伝子を含む組み合わせ
である、請求項1または2に記載の方法。

[請求項4]
 SERPINB6、NELL2、THEMIS、ZSCAN18、LAIR1、CD7、RNF130、ZIK1、LYPD3、TMEM45B、POMC、FHIT、MDS2、HOOK1、SORCS3、C2orf40、ZNF662、SPG20、ZNF717、LZTFL1、KLHL34及びBCL9遺伝子からなる群から選択される少なくとも1種の遺伝子のプロモーターCpGのDNAメチル化の有無を検出するための試薬を含む、成人T細胞白血病/リンパ腫(ATL)検出用キット。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • SAGA UNIVERSITY
  • OHARA PHARMACEUTICAL CO., LTD.
  • Inventor
  • WATANABE Tatsuro
  • SUEOKA Eizaburo
  • KIMURA Shinya
  • URESHINO Hiroshi
IPC(International Patent Classification)
Specified countries 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 JO 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 ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN WS 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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