[[WikiPathologica]]

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AITL(angioimmunoblastic T-cell lymphoma)
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>&color(red){SIZE(14){¡ü}};¡¡apoptotic bodies
>&color(red){SIZE(14){¡ü}};¡¡marginal sinus¤¬³ÈÄ¥¤¹¤ë-->dilated marginal sinus

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***AITL:¼ðáçºÙ˦¤Î¥Þ¡¼¥«¡¼ [#v94b432c]
''Follicular helper T cell(Tfh)¤Îphenotype''¤ò¼ðáçºÙ˦¤¬¼¨¤¹¡£

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-¼ðáçºÙ˦¤ÏCD4+, CD3¤¬ÍÛÀ­

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--Dorfman¤é&note{: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};''&note{: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};: 

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-- CXCL13 ¤ÈCXCR5¤Ï´Î, ç£, ¥ê¥ó¥ÑÀá ¤ª¤è¤Ó IJ´É¤Ë½Ð¸½¤·¤Æ¤¤¤ë.&note{: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&note{: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¡£&note{: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};&note{: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};&note{: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]
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--&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&note{: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]

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>'''''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)''

>
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>2. ''Hae YY et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T-cell lymphoma Nat. Genet 2014; 46(4): 371-377''


>
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-°ß´â¤Ç'''RhoA'''¤ÎÊѰۤ¬¹âÉÑÅÙ¤Ëǧ¤á¤é¤ì¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤¿.&note{: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]};&note{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};
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-'''RhoA'''ÊѰۤÏAITL/AITL´ØÏ¢¥ê¥ó¥Ñ¼ð¤È¤Ï°Û¤Ê¤ê, '''RhoA''' Y42CÊѰۤ¬ºÇ¤â¿¤¤. &note{: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]};&note{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.
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-RhoA Y42C¤Ç¤Ï, RhoA G17V¤ÈƱÍͤË, ³èÀ­·¿¤ÎGTP·ë¹ç·¿¤Ø¤ÎÊÑ´¹¤¬Äã²¼¤¹¤ë¤³¤È¤¬¼¨¤µ¤ì¤Æ¤¤¤ë.&note{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¸¥&note{: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¤·¤¿.
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-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¤¿.
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-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¤¿.
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-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¨¤·¤¿.
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-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''&note{: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};&note{:Cairns RA, IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};&note{: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. &note{:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175.};

(*2)Dobay MP et al.&note{: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)
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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'''''
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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.''};&note{: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.};&note{: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
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''PTCL¤ÎIDH2ÊÑ°Û¤ÎÆÃħ''&note{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&note{: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&note{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}; &note{Cairns:Cairns RA, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};''.
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-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''};.&note{Cairns:Cairns RA, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012 Feb 23;119(8):1901-3. PMID:22215888};&note{Sakata:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175};&note{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};
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-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''. &note{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};&note{Sakata:Sakata-Yanagimoto,M et al, Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature Genetics, 2014; 46, 171-175};&note{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};
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-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.

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'''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. &note{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};

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