[[WikiPathologica]] *Angioimmunoblastic T cell lymphoma(AITL)¤Î¿ÇÃǤȼ£ÎÅ [#b98ab9f6] lymphomania¤Î²ñ2011¹Ö±é¤è¤ê¡£ AITL(angioimmunoblastic T-cell lymphoma) ''ÆüËܤÎÁ´¥ê¥ó¥Ñ¼ð¤Î2.35%''. consultation caseÆâ¤Î³ä¹ç¤Ï¤â¤Ã¤È¹â¤¯¤Ê¤ë°õ¾Ý¡£ Angioimmunoblastic T-cell lymphoma(AITL)¡§WHO¤ÎÄêµÁ. blue book >Ž¢&color(blue){Ëö¾¿TºÙ˦(À®½ÏTºÙ˦)¥ê¥ó¥Ñ¼ð¤Î¤¦¤Á, Á´¿ÈÀ¼À´µ¤ÎÉÂÂÖ¤ò¼¨¤·, ''high endothelial venules¤Èfollicular dendritic cell¤¬Ãø¤·¤¯ÁýÀ¸¤·¤¿¥ê¥ó¥ÑÀá''¤ò¿¼ï¤Î¿»½áºÙ˦(polymorphic infiltrates)¤¬¿¯¤¹¤³¤È¤òÆÃħ¤È¤¹¤ë(WHO2008).};Ž£~ °ÊÁ°¤Ï°Û·¿È¿±þÀÁü(±ê¾É)¤È¤·¤Æ, ¥ê¥ó¥Ñ¼ð¤Ø¿Ê¹Ô¤¹¤ë¼À´µ¤È¹Í¤¨¤é¤ì, ¼ï¡¹¤Î̾¾Î¤Ç¸Æ¤Ð¤ì¤¿¤¬¸¦µæ¤Î¿ÊÊâ¤Ë¤è¤ê¸½ºß¤Ïde novo¤ËȯÀ¸¤¹¤ëËö¾¿ÀTºÙ˦¥ê¥ó¥Ñ¼ð(PTCL)¤Ç¤¢¤ë¤È¤¤¤ï¤ì¤Æ¤¤¤ë¡£ >¤¦¡¼¤ó, ¾åµ¤ÎÄêµÁ¤À¤±¤Ç¤Ï¼ÂºÝ¤Î¥ê¥ó¥ÑÀá¤òÌܤÎÁ°¤Ë¤·¤Æ¤Î¿ÇÃǤϤऺ¤«¤·¤¤¤Ê¤¢¡£ ***AITLÉÂÍý¿ÇÃǤÎclue[#w8ac45a0] ''lymphomania¤Î²ñ2011 ÃÝÆâ¸¸ãÀèÀ¸¹Ö±é¤è¤ê'' >ºÙ˦¤Ç¤Ï¥ê¥ó¥Ñµå, ÁÈ¿¥µå, ¹¥»Àµå(¹¥Ãæµå), ·Á¼ÁºÙ˦, Âç·¿ºÙ˦¤¬½Ð¸½¤¹¤ë¡£ ¥ê¥ó¥ÑÀáÇØ·Ê¤Ë¤ÏÀþ°Ý, ·ì´É, ßÉ˦¼ù¾õºÙ˦¤¬ÁýÀ¸¤·¤Æ¤¤¤ë¡£~ ¤³¤ì¤é¤¬º®ºß¤·¤Æ¡¢ºÙ˦̩ÅÙ¤ÏÄ㤤, ºÙ˦¤¬¤Ê¤¬¤ì¤ë¤è¤¦¤ËÇÛÎ󤷤Ƥ¤¤ë¡£ >¥ê¥ó¥ÑÀá¤Î½ê¸«¤Ï, ¿ºÌ¤Ç, À÷¿§¤ÏÀÖ¤¤·¹¸þ, ºÙ˦¤Ï°Õ³°¤Ë¾¯¤Ê¤¤¡£ >ºÙ˦¤¬Â¿¤¯¤Ê¤ì¤ÐPTCL-NOS¤È¡¢ºÙ˦¤¬¾¯¤Ê¤¤¤ÈHodgkin lymphoma, È¿±þÀÉÂÊѤȤδÕÊ̤Ȥʤ롣 ***AITL¿ÇÃǤؤÎÉÂÍý½ê¸«¡¡½ÅÍפʤâ¤Î¤Ï¤Ê¤Ë¡©¡§ [#fc92b290] >''A. ÀäÂФۤ·¤¤½ê¸«'' >&color(red){SIZE(14){¡ü}};¡¡&color(red){''CD21¤Ë¤è¤ë%%%ßÉ˦³°%%%FDCÁýÀ¸Áü''};(À÷¤Þ¤ê¤¬°¤±¤ì¤ÐCD23, D2-40¤ÇÀ÷¤á¤ë: &color(red){¥ê¥ó¥Ñ´ÉÆâÈé¥Þ¡¼¥«¤ÎD2-40¤ÏFDC¤Ë¤âÀ÷¤Þ¤ë};) >&color(red){SIZE(14){¡ü}};¡¡&color(red){''EBVÍÛÀºÙ˦¤Î¸ºß''};¡Ê¤Þ¤º¤ÏLMP1¤Ç²Ä, EBER-ISH¤Ê¤é¤Ê¤ª¤è¤·). &color(red){''¤Þ¤Ã¤¿¤¯¤¤¤Ê¤¤¤ÈAILT¤Î¿ÇÃǤò¹Í¤¨Ä¾¤¹¡£''}; >''B. ¤«¤Ê¤ê¤Û¤·¤¤½ê¸«'' >&color(red){SIZE(14){¡ü}};¡¡¼ðáçºÙ˦¤Ïǧ¼±¤¹¤ë¤Î¤¬º¤Æñ¡£clear cell¤¬¤¢¤ì¤Ð¼ðáçºÙ˦¡£ >&color(red){SIZE(14){¡ü}};¡¡ßÉ˦T¥Ø¥ë¥Ñ¡¼ºÙ˦¥Þ¡¼¥«(CD10, PD-1, CXCL13, etc¤Ê¤É)¤¬ÍÛÀ >''C. ¤Ê¤¯¤Æ¤â¤¤¤¤¤±¤É¤¢¤Ã¤¿¤é¤¦¤ì¤·¤¤½ê¸«'' >&color(red){SIZE(14){¡ü}};¡¡clear cell >&color(red){SIZE(14){¡ü}};¡¡burnt out germinal center >&color(red){SIZE(14){¡ü}};¡¡apoptotic bodies >&color(red){SIZE(14){¡ü}};¡¡marginal sinus¤¬³ÈÄ¥¤¹¤ë-->dilated marginal sinus >''AITL¿ÇÃǤΥҥó¥È'' >- ÉÑÅ٤Ϥޤ졣ÆüËܤÎÁ´¥ê¥ó¥Ñ¼ð¤ÎÌó2% ¤½¤ó¤Ê¤Ë½Ð²ñ¤ï¤Ê¤¤¡£ >- ǯÎð¡§&color(red){Ãæ-¹âǯÎð¼Ô};. ¼ãǯ¼Ô¤Ç¤Ï¹Í¤¨¤Ê¤ª¤¹¡£&br; LennertÀèÀ¸¤Ï''30ºÐ°Ê²¼¤Î¿Í¤ËAITL¤Î¿ÇÃǤò¤Ä¤±¤Æ¤Ï¤¤¤±¤Ê¤¤''¤È¸À¤ï¤ì¤Æ¤¤¤¿(¸Î¾®Å羡ÀèÀ¸ÃÌ) >- ǯÎð¡§&color(red){Ãæ-¹âǯÎð¼Ô};. ¼ãǯ¼Ô¤Ç¤Ï¹Í¤¨¤Ê¤ª¤¹¡£LennertÀèÀ¸¤Ï''30ºÐ°Ê²¼¤Î¿Í¤ËAITL¤Î¿ÇÃǤò¤Ä¤±¤Æ¤Ï¤¤¤±¤Ê¤¤''¤È¸À¤ï¤ì¤Æ¤¤¤¿(¸Î¾®Å羡ÀèÀ¸ÃÌ) >- &color(red){¤Û¤È¤ó¤É¤¬¿Ê¹Ô´ü¤Ç¤ß¤Ä¤«¤ë};. stageµ¤È¤¤¤ï¤ì¤ë¤ÈAITL¤Î¿ÇÃǤϡ¢¡Ö¤Û¤ó¤È¤Ë¡©¡×¤È¤Ê¤ë¡£ >- &color(red){Bulky mass¤Ï¤Û¤È¤ó¤É¤Ê¤¤};¡£¤¿¤È¤¨¤Ð½Ä³Ö¤Î10cm¤òͤ¹¤è¤¦¤Ê¼ðáî¤Ç¤ÏAITL¤Î¿ÇÃǤϡ©¤Ï¤Æ¤Ê¤È¤Ê¤ë¡£ >- ȯǮ, ÂνŸº¾¯, Åð´À¤Ê¤É¤ÎB¾É¾õ¤ò¤Ï¤¸¤á, &color(red){È鿾};, Éâ¼ð, &color(red){¶»Ê¢¿å};, ´ØÀá±ê, ´Î¼ðÂç¤Ê¤É¿ºÌ¤Ê¾É¾õ¤òÄ褹¤ë. ¸¡ººÃͤǤÏ&color(red){¹â¦Ã¥°¥í¥Ö¥ê¥ó·ì¾É};¤ä&color(red){ÉÏ·ì};¤òǧ¤á¤ë¡£ >- &color(red){''ɬ¤ºHTLV1¤¬±¢À¤Ç¤¢¤ë¤³¤È¤ò³Î¤«¤á¤ë''};.¡¡HTLV1¤Î¼ðáç¤Ï¤¢¤é¤æ¤ë¥ê¥ó¥Ñ¼ð¤ÎÁÈ¿¥Áü¤Ë¤Ë¤ë¤³¤È¤¬¤¢¤ë ***AITL:¼ðáçºÙ˦¤Î¥Þ¡¼¥«¡¼ [#v94b432c] ''Follicular helper T cell(Tfh)¤Îphenotype''¤ò¼ðáçºÙ˦¤¬¼¨¤¹¡£ Tfh cell¤ÏæõÃæ¿´¤Ë¤¤¤Æ, B-cell¤äFDC¤ÈÉѲó¤ËÁê¸ßºîÍѤ¹¤ëµ¡²ñ¤¬¤¢¤ë¡£AITLÁÈ¿¥¤Ë¤ª¤¤¤ÆB-cell, FDC¤Ï¿¿ô½Ð¸½¤·¤Æ¤¤¤ë¡£AITL¼£ÎŤËrituximab¤¬»ÈÍѤµ¤ì¸ú²Ì¤¢¤ê¤ÎÊó¹ð¤¬½Ð¤Æ¤¤¤ë¡£(¸ú²Ì¤ÎºÇ½ª³Îǧ¤Ï¤Þ¤À)¬e{:Delfau-Larue et al, Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA. Haematologica. 2012 Oct;97(10):1594-602. PMID:22371178}; -¼ðáçºÙ˦¤ÏCD4+, CD3¤¬ÍÛÀ -&color(red){Tfh cell marker ¤ÎCD10+, PD1+, BCL6+, CXCL13+, SAP¤ª¤è¤ÓICOS};¤¬¼ï¡¹¤ÎÄøÅÙ¤Ëȯ¸½¤¹¤ë¡£¬e{:Roncador G, et al. Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma. Haematologica. 2007 Aug;92(8):1059-66. Epub 2007 Jul 20.PMID:17640856};¡¡Tfh cell marker¤Îȯ¸½¤¬AILT¤ò¤Û¤«¤Îperipheral T-cell lymphoma¤È´ÕÊ̤¹¤ë¤¿¤á¤ËÍÍÑ¡£ -PanT markers; CD2, CD3, CD5, CD7. ''¤³¤ì¤é¥Þ¡¼¥«¡¼¤Ï, ¤¤¤º¤ì¤â·ç»¤·¤¦¤ë''¡£¤·¤Ð¤·¤Ð''CD5, CD7¤¬·ç»¤¹¤ë.'' -&color(blue){''PD-1(= Programmed Death-1)''};: AITL¤Î¿ÇÃÇ¥Þ¡¼¥«¡¼¡¡-->[[PD-1>Programmed cell death 1]]¤Î²òÀâ¥Ú¡¼¥¸¤Ø --ºÙ˦ÌȱÖÈ¿±þ¤Ë¤«¤«¤ï¤ë CD28 receptor family¤Î¥á¥ó¥Ð¡¼¤ÇPD-1¤ÏT, BºÙ˦¤ËÍÞÀ©Åª¤Ë¤Ï¤¿¤é¤Ëö¾¿Ìȱִ²ÍƤ˽ÅÍפÊʬ»Ò¤Ç¤¢¤ë. PD-1¤Ï''³èÀ²½TºÙ˦, BºÙ˦, ¹ü¿ñºÙ˦''¤Ëȯ¸½¤¹¤ë¡£ --Iwai¤é¬e{:Microanatomical localization of PD-1 in human tonsils. Immunol Lett. 2008; 83:215-220};¤Ë¤è¤ì¤Ð, &color(red){Ù¨Åí¤ÇPD-1¤ÏæõÃæ¿´ÌÀÎΰè¤Î¤Û¤È¤ó¤É¤ÎTºÙ˦¤È¤ï¤º¤«¤ÊBºÙ˦¤Ëȯ¸½¤¹¤ë¤Î¤ß};¤Ç¾¤ÎÉô°Ì¤Ë¤Ïȯ¸½¤·¤Æ¤¤¤Ê¤¤¡£¤³¤Îȯ¸½¤è¤êcentrocyte¤Îclonal selection¤ËPD-1¤¬´ØÍ¿¤·¤Æ¤¤¤ë¤³¤È¤¬¿ä»¡¤µ¤ì¤Æ¤¤¤ë¡£ --Dorfman¤é¬e{:Programed Death-1(PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma Dorfman DM, et al Am J Surg Pathol 30(7); 802-810: 2006};¤Ë¤è¤ì¤Ð&color(blue){23Îã¤ÎAILT¼ðáçºÙ˦¤Ë¤ÏPD-1¤¬È¯¸½¤·¤Æ¤¤¤ë};¤¬¡¢¤½¤Î¾¤ÎT, B, non-Hodgkin's lymphoma¤ä¸ÅŵŪHodgkin lymphoma¤Ë¤Ïȯ¸½¤·¤Ê¤«¤Ã¤¿¡£¤Þ¤¿&color(red){14Îã¤ÎNLPHD¤Î¼ðáçÀL&HºÙ˦¤Î¤Þ¤ï¤ê¤Ë¤ÏPD-1ÍÛÀTºÙ˦¤¬¥í¥¼¥Ã¥È¤ò·ÁÀ®¤·¤ÆÇ§¤á¤é¤ì¤¿};¡£ #br -''CXCL13 (=C-X-C motif chemokine 13. synomym: B lymphocyte chemoattractant (BLC};''¬e{:Dupuis J, et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma(AITL) A new diagnostic marker providing evidence that AITL derives from follicular helper T cells Am J Surg Pathol 30(4); 490-94¡§2006};: --CXCL13¤ÏCXC chemokine family¤Ë½ê°¤¹¤ë¾®·¿¤Î¥µ¥¤¥È¥«¥¤¥ó. paracortex¤Î¼ù¾õºÙ˦¤Ë¤è¤ë¹³¸¶Ä󼨤κÝ, ¥Ê¥¤¡¼¥ÖTºÙ˦¤Ï³èÀ²½¤·follicular/paracortical border¤Ë°Üư¤·¤ÆBºÙ˦¤Ëʬ²½¥·¥°¥Ê¥ë¤òÁ÷¤ë¡£¤³¤Î²áÄø¤òж¿Ê¤µ¤»¤ë¤Î¤¬CXCL13¤È¤½¤Î¼õÍÆÂΤǤ¢¤ë CXCR5.¡¡ÍÞÀ©¤Ë¤ÏCCR7¤Èparacortical chemokine¼õÍÆÂΤÎSLC¤ÈELC¤Ç¤¢¤ë¡£ T/BºÙ˦¤ÎÈ¿±þ¤Ï¥ê¥ó¥ÑßÉ˦¤ò·ÁÀ®¤¹¤ë¡£ßÉ˦Æâ¤ÇBºÙ˦¤Ï¤½¤Î¹³¸¶¤Ø¤Î¥¢¥Õ¥£¥Ë¥Æ¥£¡¼¤òÀ®½Ï¤µ¤», isotype switch¤ò¤ª¤³¤¹¡£¤Þ¤¿ßÉ˦¤Ë¤ÏCD4+/CXCR5+/CCR7-/CD57+¤ÎTºÙ˦¥µ¥Ö¥»¥Ã¥È¤¬Â¸ºß¤·, follicular (B) helper T cells(TSIZE(10){FH})¤È¤è¤Ð¤ì¤ë¡£TSIZE(10){FH}¤Ë¤ÏCXCL13¤¬¤Ä¤è¤¯È¯¸½¤·¤Æ¤¤¤ë¡£ -- CXCL13 ¤ÈCXCR5¤Ï´Î, ç£, ¥ê¥ó¥ÑÀá ¤ª¤è¤Ó IJ´É¤Ë½Ð¸½¤·¤Æ¤¤¤ë.¬e{:Legler DF, et al. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med 187(4); 655-60: 1998. PMID 9463416.}; CXCL13 °äÅÁ»Ò¤ÏÂè 4 À÷¿§ÂΤÎCXC chemokines clusterÆâ¤Ë¸ºß¤·¤Æ¤¤¤ë¬e{:Gunn MD, et al, A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1. Nature 391 (6669): 799-803:1998 PMID 9486651.};. -CD57¤Ï±¢À¡£ -AITLÁÈ¿¥¤Ç¤Ï, ŵ·¿Åª¤Ë''¿¿ô¤ÎBºÙ˦¤¬´Ñ»¡¤µ¤ì¤ë¡£Áý²Ã¤·¤¿BºÙ˦¤ËEBV¤Î½¸ÀѤ䥯¥í¡¼¥óÀÁý¿£¤¬Ç§¤á¤é¤ì¤ë¤³¤È¤â¤¢¤ë''¡£Î×¾²Åª¤ËAILT¤Ï·à¾É¤Î¥³¡¼¥¹¤ò¤È¤ê, ¥¯¥í¥Ê¡¼¥ë¤ÊEBVÍÛÀBºÙ˦¤¬DLBCL¤Ëž²½¤¹¤ë¤³¤È¤âµ¯¤³¤ë¤³¤È¤¬¤¢¤ë¡£¬e{:Abruzzo LV, et al. B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclona gene rearrangements associated with Epstein-Barr virus. Blood. 1993 Jul 1;82(1):241-6. PMID:8391875};¬e{:Matsue K, et al, Development of Epstein-Barr virus-associated B cell lymphoma after intensive treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinemia.Int J Hematol. 1998 Apr;67(3):319-29.PMID:9650454};¬e{:Lome-Maldonado C, et al.Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein-Barr virus infection. A different subtype of AILD-TL? Leukemia. 2002 Oct;16(10):2134-41. PMID:12357368}; ***AITL¤Ç¤Ï¼ðáçºÙ˦¤¬¾¯¤Ê¤¯Ç§¼±¤·¤Å¤é¤¤¾ì¹ç¤¬¤¢¤ë [#dde1afba] -CD4, panT markers¤Îȯ¸½¤¬·è¤Þ¤é¤Ê¤¤¤³¤È¤¬¤¢¤ë. ¤³¤Î¾ì¹ç, °Ê²¼¤Î°Û¾ïȯ¸½¥Ñ¥¿¡¼¥ó¤¬¤Æ¤¬¤«¤ê¤È¤Ê¤ë --&color(red){''æõÃæ¿´°Ê³°¤ËT''SIZE(8){FH}''(T follicular helper) cell markerÍÛÀTºÙ˦¤¬¤¤¤ë''}; --&color(red){panT marker¤Î¤É¤ì¤«¤¬·ç»¤·¤Æ¤¤¤ë};(flowcytometry¤Ç¤ï¤«¤ê¤ä¤¹¤¤) //H04-1089 //H06-1729 //H08-3917 //H11-2497 //H11-3423 //IWT cases **AITL¤Îʬ»ÒÉÂÍý³Ø¬e{:Piccaluga PP, et al. Molecular genetics of peripheral T-cell lymphomas Int J Hematol 2014; 99(3): 219-226}; [#l10af19a] ***''RHOA GTPase¤ÎÉԳ貽ÊѰۤ¬ÉѲó¤Ëǧ¤á¤é¤ì¤ë¡£ '' [#x31dede6] >RHOA¤Ï''RAS¥Õ¥¡¥ß¥ê¡¼¤Ë°¤¹¤ë¾®¤µ¤ÊGTPase ¥¿¥ó¥Ñ¥¯¼Á''¤ò¥³¡¼¥É¤¹¤ë¡£--->[[small GTPase (G-proteins) Äãʬ»ÒÎÌG¥¿¥ó¥Ñ¥¯¼Á]]¤Î¥Ú¡¼¥¸¤ò¤ß¤ë¡£ #ref(RHOA01.jpg,,80%) >'''''RHOA'''¤Ï[[Äãʬ»ÒÎÌG¥¿¥ó¥Ñ¥¯¼Á>small GTPase (G-proteins) Äãʬ»ÒÎÌG¥¿¥ó¥Ñ¥¯¼Á]]¤Ë°¤¹¤ë''¥¿¥ó¥Ñ¥¯¼Á¤ò¥³¡¼¥É¤·¡¢RHOA¤Ë·ë¹ç¤¹¤ëGDP¤¬GTP¤ËÊÑ´¹¤µ¤ì¤ë¤È²¼Î®¤Î¥¨¥Õ¥§¥¯¥¿¡¼¥¿¥ó¥Ñ¥¯¼Á¤¬³èÀ²½¤µ¤ì¤ë¡¥RHOA¤½¤ì¼«ÂΤÎGTPase³èÀ¤Ë¤è¤êGTP¤ÏGDP¤ËÊÑ´¹¤µ¤ìÉԳ貽·¿¤Ë¤â¤É¤ë¤³¤È¤Ç¡¤RHOA¤Ï''ʬ»Ò¥¹¥¤¥Ã¥Á¤È¤·¤Æµ¡Ç½¤·¤Æ¤¤¤ë''¡¥ >1. ''Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 46, 171-175 (2014)'' > -·ì´ÉÌȱֲêµåÀTºÙ˦¥ê¥ó¥Ñ¼ð¤Î71¡ó¡¤Ê¬ÎàÉÔǽ·¿¤ÎËö¾¿ÀTºÙ˦¥ê¥ó¥Ñ¼ð(PTCL-NOS)¤Î17¡ó¤Ë¤ª¤¤¤Æ¡¤RHOA°äÅÁ»Ò¤ËÊѰۤ¬Ç§¤á¤é¤ì¤¿¡¥ > -RHOA°äÅÁ»ÒÊѰۤ¬¸¡½Ð¤µ¤ì¤¿68Îã¤Î¤¦¤Á66Îã¤Ç¡¤&color(red){''17ÈÖÌܤÎGly¤¬Val¤ËÃÖ´¹¤¹¤ë(Gly17Val)''};¤È¤¤¤¦¤Þ¤Ã¤¿¤¯Æ±¤¸ÊѰۤ¬Ç§¤á¤é¤ì¤¿¡¥¤Þ¤¿¡¤¾åµ°Ê³°¤ÎTºÙ˦À¥ê¥ó¥Ñ¼ð¡¤BºÙ˦À¥ê¥ó¥Ñ¼ð¡¤¹ü¿ñ·Ï¼ðáç¤Ç¤ÏRHOA°äÅÁ»ÒÊѰۤϸ¡½Ð¤µ¤ì¤º¡¤RHOA°äÅÁ»Ò¤ÎÊѰۤϷì´ÉÌȱֲêµåÀTºÙ˦¥ê¥ó¥Ñ¼ð¤ª¤è¤ÓʬÎàÉÔǽ·¿¤ÎËö¾¿ÀTºÙ˦¥ê¥ó¥Ñ¼ð¤ËÆÃ°ÛŪ¤Ç¤¢¤ë¤³¤È¤¬¤ï¤«¤Ã¤¿¡¥ > -''TET2°äÅÁ»Ò¡¤IDH2°äÅÁ»Ò¡¤DNMT3A°äÅÁ»Ò''¤Î±ö´ðÇÛÎó¤ò¤¢¤ï¤»¤Æ·èÄꤷ¤¿·ë²Ì¡¤&color(blue){TET2°äÅÁ»Ò¤ÎÊѰۡ¤RHOA°äÅÁ»Ò¤ÎÊѰۡ¤IDH2°äÅÁ»Ò¤ÎÊѰۤΤ¢¤¤¤À¤Ë¤Ï³¬ÁØÅª¤Ê½ÅÊ£¤¬Ç§¤á¤é¤ì¤¿};¡£¤Þ¤¿¡¤''RHOA°äÅÁ»Ò¤ÎÊѰۤϥê¥ó¥Ñ¼ðºÙ˦¤ËÆÃͤǤ¢¤Ã¤¿ > -''°ìÊý¡¤''TET2°äÅÁ»Ò¤ÎÊѰۤΰìÉô¤Ï¼ðáç²½¤·¤Æ¤¤¤Ê¤¤Â¤·ìÁ°¶îºÙ˦¤Ë¤ª¤¤¤ÆÀ¸¤¸¤Æ¤¤¤ë''¤È¿ä»¡¤µ¤ì¤¿¡¥ >2. ''Hae YY et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T-cell lymphoma Nat. Genet 2014; 46(4): 371-377'' > -&color(red){RHOA protein¤ÎGTP binding region¤Î¤¦¤Á''ÊѰۤÏGly17Val¤Ë½¸Ãæ''¤·¤Æ¤¤¤ë¡£}; > -sanger sequence¤ÇÄ´¤Ù¤¿AITL45ÎãÃæ24(53.3%)¤Ëǧ¤á¤é¤ì¤¿¡£PTCL-NOS¤Ë¤Ï7.7%(1/15), NK/T cell lymphoma¤Ç¤Ï15%(3/20)¤ÎÊѰۤ¬¤¢¤Ã¤¿¡£RHOA 59-64GTP binding regionÊѰۤÏCOSMIC¤ËAITL¤Î¾¯¿ôÎãÊó¹ð¤¬¤¢¤ë¡£116-120¤Îbinding regionÊѰۤÏÊó¹ð¤µ¤ì¤Æ¤¤¤Ê¤¤¡£ > -RHOA¤ÎÊѰۤÏ178Îã¤ÎDLBCL¤Ë¤Ï¤Þ¤Ã¤¿¤¯Ç§¤á¤é¤ì¤º''T-cell lymphoma¤Ë¸ÂÄꤷ¤Æ¤¤¤ë''¤è¤¦¤Ç¤¢¤ë¡£ > -ÊѰÛÍÛÀÎã¤ÎÊѰۤÏheterozygote¤Ç¤¢¤Ã¤¿¡£ #br >''Gly17ValÊѰÛRHOA¤Ï¡¢GTPase³èÀ¤òÁÓ¼º¤·¤Æ¤¤¤ë.'' > -RhoA¤ÎG17¤Ï, K118, N117¤Ê¤É¤È¤È¤â¤ËGTP·ë¹çÉô°Ì¤ò·ÁÀ®¤·¤Æ¤¤¤ë. G17V¤Ï·ë¹çÉô°Ì¤Î¹½Â¤¤òÇ˲õ¤·, ÊѰÛÂΤÏGTP¤Ë·ë¹ç¤»¤º, ¤«¤ÄGEF(guanin exchange factor)¤È°ÂÄê¤Ë·ë¹ç¤¹¤ë.--->[[Small GTPase¤Î¥Ú¡¼¥¸>small GTPase (G-proteins) Äãʬ»ÒÎÌG¥¿¥ó¥Ñ¥¯¼Á]]¤ò¸«¤ë #br -RhoA¤ÏGTP¤Ë·ë¹ç¤¹¤ë¤³¤È¤Ç³èÀ²½¤¹¤ë¤¿¤á, RhoAG17VÊѰÛÂΤÏRhoA¥·¥°¥Ê¥ë¤È¤·¤Æ¤Ïµ¡Ç½ÁÓ¼º·¿¤È¤Ê¤ë. #br >''°ß´â¤Ç¤Î'''RhoA'''ÊѰÛ'' > -°ß´â¤Ç'''RhoA'''¤ÎÊѰۤ¬¹âÉÑÅÙ¤Ëǧ¤á¤é¤ì¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤¿.¬e{:Kakiuchi M, et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma.PMID:24816255 Nat Genet. 2014 Jun;46(6):583-7. Comment in Genetics: revealing the genomic landscape of gastric cancer. [Nat Rev Gastroenterol Hepatol. 2014]};¬e{Wang:Wang K,et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014 Jun;46(6):573-82.PMID:24816253}; #br -'''RhoA'''ÊѰۤÏAITL/AITL´ØÏ¢¥ê¥ó¥Ñ¼ð¤È¤Ï°Û¤Ê¤ê, '''RhoA''' Y42CÊѰۤ¬ºÇ¤â¿¤¤. ¬e{:Kakiuchi M, et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma.PMID:24816255 Nat Genet. 2014 Jun;46(6):583-7. Comment in Genetics: revealing the genomic landscape of gastric cancer. [Nat Rev Gastroenterol Hepatol. 2014]};¬e{Wang:Wang K,et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014 Jun;46(6):573-82.PMID:24816253}; #br -ÉÑÅÙ¤ÏÄ㤤¤¬PTCL¤Ë¤ß¤é¤ì¤ëG17¤¬¥Ð¥ê¥ó(V)¤Ç¤Ï¤Ê¤¯, ¥°¥ë¥¿¥ë»À(E)¤ËÃÖ´¹¤µ¤ì¤ëÊѰÛ(G17E)¤â°ìÄêÉÑÅÙ¤Çǧ¤á¤é¤ì¤ë. #br -RhoA Y42C¤Ç¤Ï, RhoA G17V¤ÈƱÍͤË, ³èÀ·¿¤ÎGTP·ë¹ç·¿¤Ø¤ÎÊÑ´¹¤¬Äã²¼¤¹¤ë¤³¤È¤¬¼¨¤µ¤ì¤Æ¤¤¤ë.¬e{Wang:Wang K,et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014 Jun;46(6):573-82.PMID:24816253}; >''ATLL¤ÎRhoAÊѰÛ'' > ʸ¸¥¬e{:Nagata Y, et al Variegated RHOA mutations in adult T-cell leukemia/lymphoma.Blood. 2016 Feb 4;127(5):596-604.Comment in Opposite RHOA functions within the ATLL category. [Blood. 2016] PMID:26574607}; > -ATLL203¾ÉÎã¤ò»È¤Ã¤Æ, whole genome sequencing¤Ë¤è¤ê ÆÃ°Û¤ÊRHOAÊѰۤò¸¡½Ð¤·¤¿. #br -ATLL¤Î15% (30/203)¤Ë, RHOAÊѰۤ¬Ç§¤á¤é¤ì, Á´ coding sequence¤Ë¹¤¯Ê¬ÉÛ¤·¤Æ¤¤¤¿. ¤·¤«¤·, ¿¤¯¤ÏGTP-binding pocket¤Ë¸ºß¤·, RhoA Cys16Arg¤¬ºÇ¤â¿¤¤ÊѰۤǤ¢¤Ã¤¿. #br -ÊѰۤΥ¿¥¤¥×¤äÉô°Ì¤Ë¤è¤ê, RHOAÊѰÛÂΤϰۤʤë,¶Ëü¤Ê¾ì¹ç¤ÏÈ¿ÂФκîÍѤòGTP/guanosine diphosphate (GDP)-binding kinetics, ¥¢¥¯¥Á¥óÀþ°ÝÀ©¸æ¤äž¼Ì³èÀ²½¤Ë¤ª¤¤¤Æ¼¨¤¹¤È¤¤¤¦°Õ³°¤Ê·ë²Ì¤¬Ä󼨤µ¤ì¤¿. #br -RhoA Gly17ValÊѰÛÂΤÏGTP/GDP¤Ë·ë¹ç¤»¤º, dominant negativeʬ»Ò¤È¤·¤Æ¤Õ¤ë¤Þ¤¦. °ìÊý, Cys16Arg¤ÈAla161Pro ÊѰÛÂΤÏž¼Ì³èÀ²½Â¥¿Ê¤òȼ¤¦Â®¤¤GTP/ GDP¥µ¥¤¥¯¥ê¥ó¥°¤ò¼¨¤·¤¿. #br -ATLLÇò·ìÉÂȯÀ¸¤ËRHOAµ¡Ç½¤ÎÁÓ¼º¤ª¤è¤Ó³ÍÆÀ¤ÎξÊý¤¬´ØÍ¿¤·ÆÀ¤ë¤³¤È¤ò¼¨º¶¤·¤Æ¤¤¤ë¡£¤³¤ì¤Ï, ATLL¤Îʬ»Òɰø¤Ë¤Ä¤¤¤Æ¤Î¿·¤¿¤Êƶ»¡¤òÄ󶡤¹¤ë¤À¤±¤Ç¤Ê¤¯¡¢¥Ò¥È´â¤Ë¤ª¤±¤ë°Û¼ïRHOAÊѰۤοÍͤÊÌò³ä,¤½¤Î¥æ¥Ë¡¼¥¯¤µ¤ò¶¯Ä´¤·¤Æ¤¤¤ë¡£ ***''IDH2¤Îsomatic mutation(20-47%)¤äTET2¤Îmutation(47%[40/86AITL case])¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë''¬e{:Lemonnier F, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012 Aug 16;120(7):1466-9. doi: 10.1182/blood-2012-02-408542.PMID:22760778};¬e{:Cairns RA, IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};¬e{:Odejide O, et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014 Feb 27;123(9):1293-6. doi: 10.1182/blood-2013-10-531509. Epub 2013 Dec 17.PMID:24345752}; [#q2f795ef] #ref(AITL-mutation.jpg,around,left,80%) (*1) Sakata-Yanagimoto M et al. ¬e{:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175.}; (*2)Dobay MP et al.¬e{:Dobay MP, et al.Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin.Haematologica. 2017 Apr;102(4):e148-e151.}; &color(red){RHOAÊѰÛ};¤Ï, &color(#e2041b){''ßÉ˦À¥Ø¥ë¥Ñ¡¼TºÙ˦¤ÎÆÃħ¤Î¤¢¤ëÀáÀ¥ê¥ó¥Ñ¼ðÁ´ÂΤò¥«¥Ð¡¼''};¤·¤Æ, Ìó60¡ó¤Û¤É¤Î¾ÉÎã¤Ëȯ¸½¤·¤Æ¤¤¤ë.(´¶ÅÙ ¡Á60%) °ìÊý, &color(red){IDH2ÊѰÛ};¤ÏAITL¤Î¤¦¤Á°ìÉô(30¡ó)¤Ëȯ¸½¤¹¤ë¤Î¤ß¤Ç¤¢¤ë¤¬, PTCL-NOS, FTCL¤Ë¤Ïǧ¤á¤é¤ì¤Ê¤¤. AITL¤òʬ¤±¤ë¤³¤È¤¬¤Ç¤¤ë²ÄǽÀ¤¬¤¢¤ë.~ µ¡Ç½³ÍÆÀ¡ÊÊѰۡ§R172K¤Ê¤É) #br ßÉ˦À¥Ø¥ë¥Ñ¡¼TºÙ˦¤ÎÆÃħ¤Î¤¢¤ëËö¾¿ÀTºÙ˦¥ê¥ó¥Ñ¼ð---AITL¤Ç¸«¤é¤ì¤ë°äÅÁ»Ò°Û¾ï¤ò¶¦Í; '''''TET2, DNMT3A, RHOA''''' #br Follicular T-cell lymphoma---AITL¤Ç¤ß¤é¤ì¤ë°äÅÁ»Ò°Û¾ï¤ò¶¦Í'''''TET2, DNMT3A, RHOA'''''¤¹¤ë¤Û¤«, &color(crimson){''t(5;9)(q33;q22) ITK-SYK¤¬20%¤Ëǧ¤á¤é¤ì¤ë.''};¬e{:Streubel B, et al.Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Leukemia. 2006 Feb;20(2):313-8.};¬e{:Huang Y, et al Peripheral T-cell lymphomas with a follicular growth pattern are derived from follicular helper T cells (TFH) and may show overlapping features with angioimmunoblastic T-cell lymphomas. Am J Surg Pathol. 2009 May;33(5):682-90. PMID:19295409}; ¤·ì´ï¼ðá祲¥Î¥à¸¡ºº¥¬¥¤¥É¥é¥¤¥óWeb¸ø³«ÍÑ-->[[ÆüËÜ·ì±Õ³Ø²ñWeb page¥¬¥¤¥É¥é¥¤¥ó:http://www.jshem.or.jp/modules/genomgl/]] #clear #br ''PTCL¤ÎIDH2ÊÑ°Û¤ÎÆÃħ''¬e{SakataY:ºäÅÄ(Ìø¸µ)ËãÈþ»Ò¡¡·ì´ÉÌȱֲêµåÀTºÙ˦¥ê¥ó¥Ñ¼ðȯ¾É¤Îʬ»Ò¥á¥«¥Ë¥º¥à Î×¾²·ì±Õ 2015; 56(3): 246-252}; -¹ü¿ñ·Ï¼ðáç¤ÈPTCL¤Ç¤ÏIDHÊѰۤÎʬÉÛ¤¬°Û¤Ê¤Ã¤Æ¤¤¤ë. ¹ü¿ñ·Ï¼ðáç¤Ï, IDH1, IDH2ÊѰۤÎξÊý¤¬Ç§¤á¤é¤ì¤ë¤¬, ''AITL¤Ç¤ÏIDH1ÊѰۤϤޤì¬e{:Couronné L, et al.TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012 Jan 5;366(1):95-6. PMID:22216861};¤Ç¤¢¤êIDH2ÊѰۤΤߤ¬¹âÉÑÅ٤ˤߤé¤ì¤ë¬e{Lemonnier:Lemonnier F, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012 Aug 16;120(7):1466-9.PMID:22760778}; ¬e{Cairns:Cairns RA, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};''. #br -¹ü¿ñ·Ï¼ðáç¤Ç¤ÏIDH2ÊѰۤΤ¦¤Á, R140, R172¤Î2¥«½ê¤Ë½¸Ã椷¤Æ¤¤¤ë. &color(#e2041b){''AITL¤Ë¤ª¤¤¤ÆIDH2ÊѰۤÏR172¤Ë¤Î¤ß½¸Ã椷¤Æ¤¤¤ë''};.¬e{Cairns:Cairns RA, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};¬e{Sakata:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175};¬e{Palomero:Palomero T, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas.Nat Genet. 2014 Feb;46(2):166-70.PMID:24413734}; #br -¹ü¿ñ·Ï¼ðáç¤Ë¤ª¤¤¤Æ¤Ï, TET2ÊѰۤÈIDH2ÊÑ°Û¤È¤ÏÆ±°ì¾ÉÎã¤Ç¤Ï¶¦Â¸¤·¤Ê¤¤(Áê¸ßÇÓ¾Ū)¤ÈÊ£¿ô¤ÎÊó¹ð¤¬¤¢¤ë¤¬, ''PTCL¤Ë¤ª¤¤¤Æ¤ÏTET2¤ÈIDH2ÊѰۤ϶¦Â¸¤·¤Æ¤¤¤ë''. ¬e{Lemonnier:Lemonnier F, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012 Aug 16;120(7):1466-9.PMID:22760778};¬e{Sakata:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175};¬e{Palomero:Palomero T, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas.Nat Genet. 2014 Feb;46(2):166-70.PMID:24413734}; #br -¹ü¿ñ·Ï¼ðáç¤Ç¤ÏIDH2ÊѰÛÂΤÎɸŪ¤¬¼ç¤ËTET2¤Îµ¡Ç½ÍÞÀ©¤Ç¤¢¤ë¤¿¤á¤ÈÀâÌÀ¤µ¤ì¤Æ¤¤¤ë¤¬, ''PTCL¤Ë¤ª¤¤¤Æ¤ÏIDH2ÊѰÛÂΤÎɸŪ¤¬TET2°Ê³°¤Ç¤¢¤ë''¤È¹Í¤¨¤é¤ì¤ë. #br '''TET2'''ÊѰۤˤè¤ëTET2¤Îµ¡Ç½Äã²¼¤Ïfollicular helper TºÙ˦ÍÍ¥ê¥ó¥Ñ¼ðȯ¾É¤Îȯü¤È¤Ê¤ë. °ìÊý, '''DNMT3'''¤ä'''IDH2'''ÊѰۤˤĤ¤¤Æ¤ÏTET2µ¡Ç½Äã²¼¤È·ë¤Ó¤Ä¤¯¤³¤È¤Ë¤è¤Ã¤Æ¥ê¥ó¥Ñ¼ðȯ¾É¤Ë°ìÄê¤Îµ¡Ç½¤ò²Ì¤¿¤·¤Æ¤¤¤ë¤È¹Í¤¨¤é¤ì¤ë. ¬e{SakataY:ºäÅÄ(Ìø¸µ)ËãÈþ»Ò¡¡·ì´ÉÌȱֲêµåÀTºÙ˦¥ê¥ó¥Ñ¼ðȯ¾É¤Îʬ»Ò¥á¥«¥Ë¥º¥à Î×¾²·ì±Õ 2015; 56(3): 246-252};