{"id":1744,"date":"2019-05-09T13:23:46","date_gmt":"2019-05-09T11:23:46","guid":{"rendered":"http:\/\/www.newslab.sk\/?p=1744"},"modified":"2019-05-09T13:49:02","modified_gmt":"2019-05-09T11:49:02","slug":"development-of-complex-chromosome-rearrangements-in-a-patient-with-all","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/development-of-complex-chromosome-rearrangements-in-a-patient-with-all\/","title":{"rendered":"Development of complex chromosome rearrangements in a patient with ALL"},"content":{"rendered":"

*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n

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\u00davod <\/strong><\/p>\n

Ak\u00fatna lymfoblastov\u00e1 leuk\u00e9mia (ALL) je ochorenie, ktor\u00e9 vznik\u00e1 mal\u00edgnou transform\u00e1ciou kme\u0148ovej hematopoetickej bunky lymfoidnej l\u00ednie a n\u00e1sledne doch\u00e1dza ku klon\u00e1lnej prolifer\u00e1cii lymfoidn\u00fdch prekurzorov so zastaven\u00edm diferenci\u00e1cie na r\u00f4znych stup\u0148och diferenci\u00e1cie lymfoidn\u00fdch blastov( 1). Incidencia ochorenia m\u00e1 dva vrcholy, prv\u00fd je vo veku 4 a\u017e 5 rokov s incidenciou 5,3 na 100 000 obyvate\u013eov a druh\u00fd vrchol sa nach\u00e1dza okolo 50. roku \u017eivota s incidenciou 2,3 na 100 000 obyvate\u013eov za rok(2). Klasifik\u00e1cia WHO del\u00ed ALL na B- a T-ALL pod\u013ea zasiahnutej bunkovej l\u00ednie. L\u00edniu B-ALL \u010falej rozde\u013euje na z\u00e1klade genetick\u00fdch zmien ako ne\u0161pecifikovan\u00fa alebo s rekurentn\u00fdmi genetick\u00fdmi abnormalitami (t(9;22)(q34.1;q11.2), t(v;11q23.3), t(12;21)(p13.2;q22.1), hyperdiploidia, hypodiploidia, t(5;14) (q31.1;q32.3), t(1;19)(q23;p13.3)(3). Stanovenie chromoz\u00f3mov\u00fdch aber\u00e1ci\u00ed m\u00e1 pri leuk\u00e9mii ve\u013ek\u00fd v\u00fdznam pre progn\u00f3zu a podanie spr\u00e1vnej lie\u010dby. Typick\u00e9 chromoz\u00f3mov\u00e9 aber\u00e1cie sa l\u00ed\u0161ia v z\u00e1vislosti od veku pacienta a tie\u017e bunkovej l\u00ednie.<\/p>\n

ALL je naj\u010dastej\u0161ia malignita detsk\u00fdch pacientov a vyskytuj\u00fa sa pri nej typick\u00e9 aber\u00e1cie ako t(12;21), t(1;19) a hyperploidia, ktor\u00e9 s\u00fa u dospel\u00fdch s touto diagn\u00f3zou pozorovan\u00e9 len zriedka(4). Naopak, u dospel\u00fdch ALL predstavuje len 20 % v\u0161etk\u00fdch leuk\u00e9mi\u00ed(5). Okolo 70 % dospel\u00fdch s ALL m\u00e1 leukemick\u00e9 bunky s chromoz\u00f3mov\u00fdmi abnormalitami. Naj\u010dastej\u0161iu aber\u00e1ciu predstavuje t(9;22). Pri t(9;22) doch\u00e1dza k zlomom a v\u00fdmene \u010dast\u00ed dlh\u00fdch ramien 9. a 22. chromoz\u00f3mu, \u010d\u00edm vznik\u00e1 f\u00fazny g\u00e9n BCR-ABL. <\/em>F\u00fazny prote\u00edn produkovan\u00fd z tohto g\u00e9nu je akt\u00edvny onkoprote\u00edn s tyroz\u00ednkin\u00e1zovou aktivitou, ktor\u00fd d\u00e1va leukemick\u00fdm bunk\u00e1m prolifera\u010dn\u00fa v\u00fdhodu. Pod\u013ea konkr\u00e9tneho miesta zlomu a procesovania mRNA m\u00f4\u017ee vznika\u0165 hybridn\u00fd prote\u00edn BCR-ABL s ve\u013ekos\u0165ou 210 kDa (p210), 190 kDa (p190) a 230kDa (p230). Pacienti s B-ALL maj\u00fa pr\u00edtomn\u00fd p190 (sk\u00f4r u det\u00ed) alebo p210 (\u010dastej\u0161ie u dospel\u00fdch). Klinick\u00e9 znaky u pacientov s B-ALL p190 a p210 boli ve\u013emi podobn\u00e9, mierne hor\u0161\u00ed klinick\u00fd v\u00fdsledok bol pozorovan\u00fd u pacientov s p210(6). Translok\u00e1cia t(9;22) existuje v dvoch form\u00e1ch \u2013 v jednoduchej a variantnej. V jednoduchej sa na nej z\u00fa\u010dast\u0148uj\u00fa len dva chromoz\u00f3my 9 a 22, a variantn\u00e1 zah\u0155\u0148a okrem spom\u00ednan\u00fdch chromoz\u00f3mov aj \u010fal\u0161\u00ed. Tyroz\u00ednkin\u00e1zov\u00e9 inhib\u00edtory ako lie\u010div\u00e1 vhodn\u00e9 pri klasickej t(9;22) s\u00fa \u00fa\u010dinn\u00e9 aj pre variantn\u00e9 formy(7,8).<\/p>\n

Pri ak\u00fatnych leuk\u00e9mi\u00e1ch je \u010dasto zaznamenan\u00e1 nadexpresia g\u00e9nu WT1. <\/em>G\u00e9n WT1 <\/em>sa nach\u00e1dza na kr\u00e1tkom ramene 11. chromoz\u00f3mu v oblasti 11p13. Ako transkrip\u010dn\u00fd faktor m\u00e1 d\u00f4le\u017eit\u00fa \u00falohu pri kontrole prolifer\u00e1cie, diferenci\u00e1cie a pri apopt\u00f3ze. Stupe\u0148 jeho expresie je obzvl\u00e1\u0161\u0165 v\u00fdznamn\u00fd pri hematopo\u00e9ze, ke\u010f je g\u00e9n exprimovan\u00fd v nezrel\u00fdch bunk\u00e1ch, a a\u017e po jeho poklese m\u00f4\u017ee d\u00f4js\u0165 k matur\u00e1cii krvn\u00fdch elementov(9,10). Samotn\u00fd g\u00e9n WT1 <\/em>predstavuje ne\u0161pecifick\u00fd marker, ke\u010f\u017ee sa nesp\u00e1ja len s jedn\u00fdm typom leuk\u00e9mie, av\u0161ak sl\u00fa\u017ei ako terapeutick\u00fd cie\u013e a znak na monitorovanie minim\u00e1lnej rezidu\u00e1lnej choroby(9). Progn\u00f3za ALL sa odv\u00edja od viacer\u00fdch faktorov a zhor\u0161uje sa s opakovan\u00fdmi atakmi leuk\u00e9mie na jedinca. \u0160ancu na kompletn\u00fa remisiu zni\u017euje vek pacienta, zn\u00ed\u017een\u00e1 tolerancia lie\u010dby a vy\u0161\u0161\u00ed po\u010det leukocytov.<\/p>\n

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Kazuistika <\/strong><\/p>\n

Mu\u017ea vo veku 63 rokov v po\u010diatku anamn\u00e9zy v d\u00f4sledku epidermoidn\u00e9ho karcin\u00f3mu pravej podnebnej mandle sledoval jeho sp\u00e1dov\u00fd onkol\u00f3g. Pacient podst\u00fapil chemoterapiu a r\u00e1dioterapiu, \u010do pravdepodobne n\u00e1sledne vyvolalo myeloproliferat\u00edvnu neopl\u00e1ziu (MPN) s nepr\u00edtomn\u00fdm filadelfsk\u00fdm chromoz\u00f3mom (Ph). Od roku 2009 je veden\u00fd v hematologickej ambulancii s diagn\u00f3zou esenci\u00e1lna trombocyt\u00e9mia. V roku 2014 mu bola diagnostikovan\u00e1 sekund\u00e1rna myelofibr\u00f3za. \u00a0<\/strong>O 3 roky, v roku 2017, bol u pacienta zaznamenan\u00fd prechod do B-bunkovej ALL. Na z\u00e1klade pr\u00edtomnosti 21 % patologickej popul\u00e1cie B-lymfoblastov a na z\u00e1klade imunofenotypu (pr\u00edtomn\u00e9 znaky CD10, CD19, TdT a nepr\u00edtomn\u00fd CD117) bola u pacienta potvrden\u00e1 B-ALL. Vzorky kostnej drene (KD) a perif\u00e9rnej krvi (PK) sme v na\u0161om laborat\u00f3riu prv\u00fdkr\u00e1t vy\u0161etrili v okt\u00f3bri 2017. Na z\u00e1klade genetickej anal\u00fdzy boli zaznamenan\u00e9 patologick\u00e9 n\u00e1lezy spojen\u00e9 s nepriaznivou progn\u00f3zou. Leuk\u00e9mia u pacienta progredovala, na \u010do bola podan\u00e1 siln\u00e1 lie\u010dba, ktor\u00e1 viedla k hemotoxick\u00e9mu \u0161oku a bol zaznamenan\u00fd zhor\u0161en\u00fd hematokryt.<\/p>\n

Na obr\u00e1zku 1 <\/em><\/strong>je zn\u00e1zornen\u00fd v\u00fdvoj lie\u010dby u pacienta. Progn\u00f3za je moment\u00e1lne priazniv\u00e1, preto\u017ee pacient sa nach\u00e1dza v stave remisie bez blastov.<\/p>\n

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Met\u00f3dy <\/strong><\/p>\n

Cytogenetick\u00e1 anal\u00fdza bola uskuto\u010dnen\u00e1 na vzork\u00e1ch kostnej drene, spracovan\u00fdch pod\u013ea \u0161tandardn\u00fdch cytogenetick\u00fdch postupov po 24-hodinovej kultiv\u00e1cii. Prepar\u00e1ty boli farben\u00e9 Wrightov\u00fdm roztokom. N\u00e1sledne bolo hodnoten\u00fdch 20 metaf\u00e1z vo svetelnom mikroskope, ak to kvalita vzorky umo\u017enila, a karyotyp bol zap\u00edsan\u00fd pod\u013ea International system for human cytogenetic nomenclature <\/em>(ISCN)(12). Fluorescen\u010dn\u00e1 in situ <\/em>hybridiz\u00e1cia (FISH) sa uskuto\u010dnila na vzork\u00e1ch KD alebo PK spracovan\u00fdch pod\u013ea \u0161tandardn\u00fdch postupov. Na detekciu aber\u00e1ci\u00ed na chromoz\u00f3moch 2, 7, 9 a 22 boli pou\u017eit\u00e9 \u0161pecifick\u00e9 lokusov\u00e9 sondy a celochromoz\u00f3mov\u00e9 sondy (WCPs). Preh\u013ead sond je op\u00edsan\u00fd v tabu\u013eke 1<\/em><\/strong>. Vo fluorescen\u010dnom mikroskope bolo hodnoten\u00fdch 200 jadier. Molekulov\u00e1 anal\u00fdza bola uskuto\u010dnen\u00e1 pomocou met\u00f3dy RT-PCR. Na detekciu g\u00e9nov WT1 <\/em>a BCR-ABL <\/em>bol pou\u017eit\u00fd kitQiagen (Dynex).<\/p>\n

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V\u00fdsledky <\/strong><\/p>\n

Vzorka pacienta bola vy\u0161etrovan\u00e1 v na\u0161om laborat\u00f3riu doposia\u013e \u0161tyrikr\u00e1t. Prv\u00e9 vy\u0161etrenie KD a PK sa uskuto\u010dnilo v okt\u00f3bri roku 2017 po prechode do ALL. Preh\u013ead vy\u0161etren\u00ed a ich v\u00fdsledkov sa nach\u00e1dza v tabu\u013eke 2<\/em><\/strong>.<\/p>\n

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Cytogenetick\u00e9 a FISH vy\u0161etrenie <\/strong><\/p>\n

Cytogenetickou anal\u00fdzou sme pri prvom vy\u0161etren\u00ed odhalili variantn\u00fa formu translok\u00e1cie t(9;22) chromoz\u00f3mu, ke\u010f okrem chromoz\u00f3mov 9, 22 je do translok\u00e1cie zahrnut\u00fd aj tret\u00ed \u2013 chromoz\u00f3m 2. Do\u0161lo k inzercii \u010dasti kr\u00e1tkych ramien chromoz\u00f3mu 2 do chromoz\u00f3mu 9 v oblasti 9q34. Stanovili sme karyotyp 46, XY, der(9)t(9;22)(q34;q11)ins(9;2) (q34;p15p23) (obr\u00e1zok 2)<\/em><\/strong>. Chromoz\u00f3mov\u00e9 aber\u00e1cie pozorovan\u00e9 na karyotype (obr\u00e1zok 2) <\/em><\/strong>sme potvrdili FISH met\u00f3dou. V 97 % jadier bola pr\u00edtomn\u00e1 BCR-ABL <\/em>f\u00fazia (obr\u00e1zok 3)<\/em><\/strong>. Pomocou celochromoz\u00f3mov\u00fdch sond WCP 2 a WCP 9 sme odhalili inzerciu kr\u00e1tkych ramien chromoz\u00f3mu 2 do dlh\u00fdch ramien chromoz\u00f3mu 9 (obr\u00e1zok 4)<\/em><\/strong>. Pri kontrolnom vy\u0161etren\u00ed po 6 mesiacoch sa napriek lie\u010dbe v patologickom klone okrem predch\u00e1dzaj\u00facich zmien objavila aj sekund\u00e1rna aber\u00e1cia v podobe dic(7;9). Pacient nemal ani jeden zdrav\u00fd 9. chromoz\u00f3m.<\/p>\n

Karyotyp pacienta (obr\u00e1zok 5) <\/em><\/strong>sme ur\u010dili ako 45, XY, dic(7;9)(p11;p11), der(9)t(9;22) (q34;q11)ins(9;2)(q34;p15p23). FISH vy\u0161etrenie potvrdilo dic(7;9) pomocou \u0161pecifick\u00fdch lokusov\u00fdch sond c7\/7q22\/7q36 a 9c\/9p16 (obr\u00e1zok 6)<\/em><\/strong>. Centrom\u00e9ry chromoz\u00f3mu 7 (obr\u00e1zok 7a) <\/em><\/strong>a 9 boli obe pr\u00edtomn\u00e9, na z\u00e1klade \u010doho sme potvrdili dicentrick\u00fd chromoz\u00f3m. \u0160pecifickou lokusovou sondou sme z\u00e1rove\u0148 detegovali del\u00e9ciu kr\u00e1tkeho ramena chromoz\u00f3mu 9 v oblasti p16 (obr\u00e1zok 7 b)<\/em><\/strong>, \u010do n\u00e1m nepriamo potvrdzuje pr\u00edtomnos\u0165 dicentra zlo\u017een\u00e9ho z dlh\u00fdch ramien chromoz\u00f3mov 7 a 9 a z\u00e1rove\u0148 n\u00e1m umo\u017e\u0148uje uskuto\u010d\u0148ova\u0165 \u010fal\u0161ie vy\u0161etrenia na interf\u00e1zov\u00fdch jadr\u00e1ch a sledova\u0165 monoz\u00f3miu 9p. Nasleduj\u00faca kontrola (6\/2018) sa uskuto\u010dnila z perif\u00e9rnej krvi pomocou FISH anal\u00fdzy. Bola odhalen\u00e1 pr\u00edtomnos\u0165 2 klonov translok\u00e1cie 9;22 \u2013 klasick\u00fd \u2013 postihuj\u00faci len dva chromoz\u00f3my, 9 a 22, a klon s variatnou translok\u00e1ciou der(9) t(9;22)(q34;q11)ins(9;2) (rovnakou ako pri prvom n\u00e1leze). Posledn\u00e1 kontrola (8\/2018) sa uskuto\u010dnila zo vzorky kostnej drene. Cytogenetick\u00e1 anal\u00fdza nebola mo\u017en\u00e1 pre ne\u00faspe\u0161n\u00fa kultiv\u00e1ciu a FISH anal\u00fdza potvrdila negat\u00edvny v\u00fdsledok na pr\u00edtomnos\u0165 t(9;22).<\/p>\n

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Molekulov\u00e1 anal\u00fdza <\/strong><\/p>\n

Molekulovou anal\u00fdzou bol u pacienta detegovan\u00fd f\u00fazny transkript BCR-ABL p210 pri v\u0161etk\u00fdch vy\u0161etreniach. Hladina jeho expresie sa v danom \u010dase menila a najvy\u0161\u0161ia hodnota bola zaznamenan\u00e1 pri druhej kontrole (4\/2018), n\u00e1sledne u\u017e pr\u00edtomnos\u0165 f\u00fazneho transkriptu rap\u00eddne klesala (graf 1)<\/em><\/strong>. F\u00fazny g\u00e9n mo\u017eno kvantifikova\u0165 pomocou NCN, \u010do predstavuje pomer po\u010dtu k\u00f3pi\u00ed f\u00fazneho g\u00e9nu k po\u010dtu k\u00f3pi\u00ed kontroln\u00e9ho g\u00e9nu (tabu\u013eka 2)<\/em><\/strong>. \u00a0<\/strong>Pacientovi bol analyzovan\u00fd stav expresie g\u00e9nu WT1. Fyziologick\u00e1 hodnota zo vzorky kostnej drene je 0,01 \u2013 0,04, v perif\u00e9rnej krvi je to 0,002. Nadexpresia g\u00e9nu WT1 bola pozit\u00edvna pri prv\u00fdch dvoch vy\u0161etreniach a podobne ako pri ostatn\u00fdch v\u00fdsledkoch bolo mo\u017en\u00e9 pozorova\u0165 zhor\u0161enie stavu pacienta pr\u00e1ve pri druhom, ke\u010f hladina expresie v kostnej dreni st\u00fapla z 0,057 na 0,09. N\u00e1sledne pacient za\u010dal reagova\u0165 na lie\u010dbu a jeho stav sa zlep\u0161il.<\/p>\n

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Diskusia <\/strong><\/p>\n

Pacientovi bola stanoven\u00e1 diagn\u00f3za B-ALL. Pre B-ALL je typick\u00e1 pr\u00edtomnos\u0165 znakov CD10, CD19 a TdT a z\u00e1rove\u0148 nepr\u00edtomnos\u0165 CD117(11), \u010do koreluje s na\u0161imi v\u00fdsledkami, u pacienta boli toti\u017e imunologickou fenotypiz\u00e1ciou pr\u00edtomn\u00e9 znaky CD10 (92 %), CD19 (100 %) a TdT (93 %). Naj\u010dastej\u0161ou chromoz\u00f3movou aber\u00e1ciou pri ochoren\u00ed B-ALL u dospel\u00fdch je t(9;22). T\u00e1to aber\u00e1cia, \u010di u\u017e klasick\u00e1, alebo variantn\u00e1, je pri B-ALL spojen\u00e1 so zlou progn\u00f3zou. N\u00e1zory na biologick\u00fa funkciu klasickej a variantnej formy sa r\u00f4znia. Ist\u00e9 \u0161t\u00fadie nazna\u010duj\u00fa, \u017ee pacienti s variantnou formou maj\u00fa hor\u0161ie v\u00fdsledky, av\u0161ak existuj\u00fa aj protichodn\u00e9 n\u00e1zory, pod\u013ea ktor\u00fdch tak\u00e9to translok\u00e1cie nemaj\u00fa vplyv na v\u00fdsledok lie\u010dby a pre\u017e\u00edvanie(13,14). Na z\u00e1klade anal\u00fdzy genetick\u00fdch v\u00fdsledkov sa mo\u017eno domnieva\u0165, \u017ee pacient mal p\u00f4vodne klasick\u00fa t(9;22), ktor\u00e1 bola detegovan\u00e1 pri pozit\u00edvnej reakcii pacienta na lie\u010dbu, ke\u010f do\u0161lo k poklesu buniek s patologick\u00fdm klonom z 97 % a 20 %. Pri druhom kontrolnom vy\u0161etren\u00ed (4\/2018) pribudol k p\u00f4vodn\u00e9mu n\u00e1lezu dic(7;9). V patologickom klone sa u pacienta nenach\u00e1dzal ani jeden 9. chromoz\u00f3m, ktor\u00fd by nebol pozna\u010den\u00fd chromoz\u00f3movou prestavbou. Kr\u00e1tke ramen\u00e1 7p a 9p obsahuj\u00fa tumor\u00f3zne supresorov\u00e9 g\u00e9ny a pod\u013ea hypot\u00e9zy ich strata vedie k leukemogen\u00e9ze. Samotn\u00e1 pr\u00edtomnos\u0165 dic(7;9) pri diagn\u00f3ze B-ALL ovplyv\u0148uje progn\u00f3zu, pri\u010dom z\u00e1vis\u00ed najm\u00e4 od veku pacienta. Detsk\u00fd pacient m\u00e1 pod\u013ea literat\u00fary priazniv\u00fa progn\u00f3zu a dospel\u00fd, naopak, nepriazniv\u00fa. Pri dospel\u00fdch pacientoch sa za naj\u00faspe\u0161nej\u0161iu lie\u010dbu pova\u017euje transplant\u00e1cia kostnej drene, ak to celkov\u00fd zdravotn\u00fd stav pacienta dovo\u013euje(15,16,17).<\/p>\n

Okolo 70 % dospel\u00fdch pacientov s ALL a t(9;22) m\u00e1 aj sekund\u00e1rne chromoz\u00f3mov\u00e9 aber\u00e1cie. Naj\u010dastej\u0161ie ide o +der(22)t(9;22), +21, abnormality 9p, vysok\u00fa hyperploidiu (viac ako 50 chromoz\u00f3mov), +8, \u20137, +X, zmeny na 8. chromoz\u00f3me, nadbytok \u010dasti 1q alebo stratu 7p. Progn\u00f3za sa l\u00ed\u0161i v z\u00e1vislosti od konkr\u00e9tnej sekund\u00e1rnej aber\u00e1cie(14). V \u0161t\u00fadii Pan a kol. (2006) mali 4 zo 7 pacientov s\u00fa\u010dasne obe spomenut\u00e9 chromoz\u00f3mov\u00e9 aber\u00e1cie. Traja pacienti boli lie\u010den\u00ed chemoterapiou a jeden podst\u00fapil transplant\u00e1ciu kostnej drene, d\u013a\u017eka ich pre\u017eitia bola od 8 do 14,5 mesiaca(17). Zlep\u0161enie stavu n\u00e1\u0161ho pacienta napriek zlej progn\u00f3ze si od\u00f4vod\u0148ujeme vhodnou lie\u010dbou, ktor\u00e1 bola pacientovi podan\u00e1 v spr\u00e1vnom \u010dase. D\u00f4le\u017eit\u00e9 je na\u010falej sledova\u0165 pacienta a v skorom \u0161t\u00e1diu podchyti\u0165 relaps.<\/p>\n

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Z\u00e1ver <\/strong><\/p>\n

Komplexn\u00e1 prestavba chromoz\u00f3mov bola pozorovan\u00e1 u 63-ro\u010dn\u00e9ho pacienta, ktor\u00fd prekonal prechod Ph negat\u00edvnej MPN na Ph pozit\u00edvnu B-bunkov\u00fa ALL. Pacient podst\u00fapil chemoterapiu, na ktor\u00fa zareagoval hemotoxick\u00fdm \u0161okom, preto mu musela by\u0165 zn\u00ed\u017een\u00e1 d\u00e1vka lie\u010div. Po n\u00e1slednom stabilizovan\u00ed krvn\u00e9ho obrazu sa stav pacienta zlep\u0161il a moment\u00e1lne je v stave remisie. Pre predch\u00e1dzaj\u00faci cytogenetick\u00fd n\u00e1lez s nepriaznivou progn\u00f3zou je pre n\u00e1s tento pr\u00edpad zauj\u00edmav\u00fd a napriek stavu remisie je na\u010falej nutn\u00e9 pacienta pravidelne monitorova\u0165.<\/p>\n

 <\/p>\n

Po\u010fakovanie: <\/em><\/strong>Rada by som sa touto cestou po\u010fakovala v\u0161etk\u00fdm kolegom, ktor\u00ed spolupracovali na vy\u0161etren\u00ed pacienta, a MUDr. Hatalovej za osobn\u00fa konzult\u00e1ciu.<\/em><\/p>\n

 <\/p>\n

\u00a0<\/em>LITERAT\u00daRA <\/strong><\/p>\n

    \n
  1. http:\/\/www.hematology.sk\/docs\/ALL_2017.pdf<\/a><\/li>\n
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  8. Sawalha Y, Advani AS. Management of older adults with acute lymphoblastic leukemia: challenges and current approaches. International Journal of Hematologic Oncology 2018; 7(1).<\/li>\n
  9. Busse A, Gokbuget N, Siehl JM, et al. Wilms\u2019 tumor gene 1 (WT1) expression in subtypes of acute lymphoblastic leukemia (ALL) of adults and impact on clinical outcome. Ann Hematol 2009; 88: 1199-1205.<\/li>\n
  10. Ellisen LW, Carlesso N, Cheng T, et al. The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO Journal 2001; 20(8): 1897-1909.<\/li>\n
  11. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th Edition. Lyon: WHO 2017. 202p.<\/li>\n
  12. McGowan-Jordan J, Simons A, Schmid M. ISCN An International System for Human Cytogenomic Nomenclature. Paris: Karger 2016.<\/li>\n
  13. Marzocchi G, Castagnetti F, Luatti S, et al. Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis. Blood 2011; 117: 6793-6800.<\/li>\n
  14. Wetzler M, Dodge RK, Mr\u00f3zek K, et al. Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B. British Journal of Haematology 2004; 124: 275-288.<\/li>\n
  15. Thomas X, Olteanu N, Charrin C, et al. Acute lymphoblastic leukemia in the elderly: The Edouard Herriot Hospital Experimence. Am J Hematol 2001; 67(2): 73-83.<\/li>\n
  16. Raimondi SC, Zhou Y, Mathew S, et al. Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer 2003; 98(12): 2715-22.<\/li>\n
  17. Pan J, Xue Y, Wu Y, et al. Dicentric (7;9)(p11;p11) is a rare but recurrent abnormality in acute lymphoblastic leukemia: a study of 7 cases. Cancer Genet Cytogenet 2006; 169(2006): 159-63.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.     \u00davod Ak\u00fatna lymfoblastov\u00e1 leuk\u00e9mia (ALL) je ochorenie, ktor\u00e9 vznik\u00e1 mal\u00edgnou transform\u00e1ciou kme\u0148ovej hematopoetickej bunky lymfoidnej l\u00ednie a n\u00e1sledne doch\u00e1dza ku klon\u00e1lnej prolifer\u00e1cii lymfoidn\u00fdch prekurzorov so zastaven\u00edm diferenci\u00e1cie na<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[1217,1211,803,1218],"class_list":["post-1744","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-acute-lymphocytic-leukaemia","tag-bcr-abl","tag-cytogenetics","tag-dicentric-chromosome","typ_clanku-casuistry"],"acf":{"abstrakt":"

    In the report, we describe an interesting case of 63-year old man with diagnosis of acute lymphoblastic leukaemia. We examined karyotype with cytogenetic methods and identified variant of t(9;22) with the chromosome 2. After 6 months, furthermore, we noticed dic(7;9). We determine the karyotype of the patient 45, XY, dic(7;9) (p11;p11), der(9)t(9;22)(q34;q11)ins(9;2)(q34;p15p23), which is linked with poor prognosis. Despite this fact, our patient is in remission after the treatment. <\/p>\n

    Keywords: acute lymphocytic leukaemia, cytogenetics, FISH, BCR-ABL, dicentric chromosome <\/p>\n","casopis":[{"ID":1633,"post_author":"7","post_date":"2019-05-09 08:56:48","post_date_gmt":"2019-05-09 06:56:48","post_content":"

      \r\n \t
    • Primary pancreatic liposarcoma \u2013 the case report and iterature review<\/li>\r\n \t
    • DNA sequencing in laboratory diagnostics of bacterial pathogens<\/li>\r\n \t
    • Importance and diagnostic of anti-phospholipid antibodies in women with reproductive disorders<\/li>\r\n \t
    • Development of complex chromosome rearrangements in a patient with ALL<\/li>\r\n \t
    • HCV infection \u2013 more than 20 years of drug development<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-3","to_ping":"","pinged":"","post_modified":"2019-05-09 08:56:48","post_modified_gmt":"2019-05-09 06:56:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/?post_type=casopis&p=1633","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"51-55","upload_clanok":{"ID":1745,"id":1745,"title":"V\u00fdvoj komplexn\u00fdch chromoz\u00f3mov\u00fdch prestavieb u pacienta s ALL","filename":"V\u00fdvoj-komplexn\u00fdch-chromoz\u00f3mov\u00fdch-prestavieb-u-pacienta-s-ALL.pdf","filesize":260051,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2019\/05\/V\u00fdvoj-komplexn\u00fdch-chromoz\u00f3mov\u00fdch-prestavieb-u-pacienta-s-ALL.pdf","link":"https:\/\/www.newslab.sk\/en\/development-of-complex-chromosome-rearrangements-in-a-patient-with-all\/vyvoj-komplexnych-chromozomovych-prestavieb-u-pacienta-s-all\/","alt":"","author":"7","description":"","caption":"","name":"vyvoj-komplexnych-chromozomovych-prestavieb-u-pacienta-s-all","status":"inherit","uploaded_to":1744,"date":"2019-05-09 11:20:40","modified":"2019-05-09 11:20:40","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1744","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1744"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1744\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1744"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1744"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1744"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}