{"id":1182,"date":"2017-01-31T16:59:39","date_gmt":"2017-01-31T15:59:39","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/31\/aberacie-chromozomu-11-u-pacientky-s-akutnou-myeloidnou-leukemiou-kazuistika\/"},"modified":"2017-10-04T14:55:38","modified_gmt":"2017-10-04T12:55:38","slug":"chromosome-11-aberrations-in-a-patient-with-acute-myeloid-leukemia-a-case-study","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/chromosome-11-aberrations-in-a-patient-with-acute-myeloid-leukemia-a-case-study\/","title":{"rendered":"Chromosome 11 Aberrations in a Patient with Acute Myeloid Leukemia: A Case Study"},"content":{"rendered":"<pre><strong><span style=\"color: #ff0000;\">*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0<\/span>\r\n<span style=\"color: #ff0000;\">attachment at the end of the paper.<\/span>\r\n<\/strong><\/pre>\n<p>&nbsp;<\/p>\n<p><strong>\u00da<\/strong><strong>vod<\/strong><\/p>\n<p>Ak\u00fatne myeloidn\u00e9 leuk\u00e9mie (AML) predstavuj\u00fa heterog\u00e9nnu skupinu mal\u00edgnych ochoren\u00ed charakterizovan\u00fdch nekontrolovanou prolifer\u00e1ciou a akumul\u00e1ciou nezrel\u00fdch hematopoetick\u00fdch\u00a0 buniek v kostnej dreni (KD) a n\u00e1sledn\u00fdm vyplavovan\u00edm do perif\u00e9rnej krvi (PK). Doch\u00e1dza \u00a0ku klon\u00e1lnej expanzii myeloblastov, ktor\u00e9 tvoria \u2265 20 % buniek v kostnej dreni alebo v perif\u00e9rnej krvi. AML predstavuje 2 \u2013 4 % v\u0161etk\u00fdch mal\u00edgnych n\u00e1dorov a incidencia ochorenia je 2 \u2013 3 pr\u00edpady na 100 000 obyvate\u013eov\/rok. AML sa vyskytuje sa vo v\u0161etk\u00fdch vekov\u00fdch skupin\u00e1ch, av\u0161ak s vekom v\u00fdskyt ochorenia st\u00fapa a incidencia nad 65 rokov je 12 \u2013 15 pr\u00edpadov na 100 000 obyvate\u013eov a je mierne vy\u0161\u0161ia u mu\u017eov ako u \u017eien (1).<\/p>\n<p>D\u00f4le\u017eit\u00fdmi determinantmi AML s\u00fa cytogenetick\u00e9 zmeny. V \u010dase diagn\u00f3zy sa vyskytuj\u00fa klon\u00e1lne chromoz\u00f3mov\u00e9 aber\u00e1cie pribli\u017ene u 50 a\u017e 60 % pacientov. Pacientov m\u00f4\u017eeme na z\u00e1klade klinick\u00fdch a genetick\u00fdch znakov rozdeli\u0165 do troch prognostick\u00fdch skup\u00edn (2):<\/p>\n<ul>\n<li>s priaznivou progn\u00f3zou \u2013 t(8;21), t(15;17), inv(16),<\/li>\n<li>so strednou progn\u00f3zou \u2013 norm\u00e1lny\u00a0 karyotyp, t(9;11), del(11q), del(7q), del(9q), del(20q), +8,+11,+13,+21,<\/li>\n<li>s nepriaznivou progn\u00f3zou \u2013 komplexn\u00fd karyotyp, prestavby 11q23, inv(3)\/t(3;3).<\/li>\n<\/ul>\n<p>\u010cast\u00fdm cie\u013eom prestavieb v hematologick\u00fdch \u00a0malignit\u00e1ch \u00a0je g\u00e9n <em>K<\/em><em>M<\/em><em>T2<\/em><em>A \u00a0<\/em>(star\u0161\u00ed n\u00e1zov <em>ML<\/em><em>L<\/em>) lokalizovan\u00fd na chromoz\u00f3me \u00a011 v oblasti 11q23. Je to protoonkog\u00e9n s d\u013a\u017ekou 89 kb, pozost\u00e1vaj\u00faci \u00a0z 36 ex\u00f3nov. K\u00f3duje jadrov\u00fd prote\u00edn s 430 kDa, ktor\u00fd m\u00e1 d\u00f4le\u017eit\u00fa \u00falohu v regul\u00e1cii transkripcie <em>H<\/em><em>O<\/em><em>X <\/em>g\u00e9nov, ktor\u00e9 participuj\u00fa na kontrole embryon\u00e1lneho \u00a0v\u00fdvoja a na diferenci\u00e1cii hematopoetick\u00fdch \u00a0buniek (3, 4).<\/p>\n<p>Reciprok\u00e9 translok\u00e1cie predstavuj\u00fa naj\u010dastej\u0161iu formu prestavby <em>K<\/em><em>MT2A <\/em>g\u00e9nu u pacientov s AML. 11q23 lokus je vysoko promiskuitn\u00fd a v s\u00fa\u010dasnosti je identifikovan\u00fdch viac ako 70 r\u00f4znych f\u00faznych partnerov, s ktor\u00fdmi sa vyskytuje v prestavbe. F\u00fazny g\u00e9n vznik\u00e1 f\u00faziou 5\u00b4-konca <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>g\u00e9nu a 3\u00b4-konca partnersk\u00e9ho g\u00e9nu. V\u00fdsledn\u00fd f\u00fazny prote\u00edn sp\u00f4- sobuje zmenu fyziologick\u00fdch vlastnost\u00ed MLL prote\u00ednu, \u010do m\u00e1 za n\u00e1sledok leukemick\u00fa transform\u00e1ciu prekurzorov\u00fdch hematopoetick\u00fdch buniek (5). Progn\u00f3za \u00a0translok\u00e1cie \u00a0z\u00e1vis\u00ed od f\u00fazneho partnera, av\u0161ak pri v\u00e4\u010d\u0161ine prestavieb je nepriazniv\u00e1 (4, 6).<\/p>\n<p>Del\u00e9cie dlh\u00e9ho ramena chromoz\u00f3mu \u00a011 patria \u00a0k zriedkavej\u0161\u00edm \u00a0cytogenetick\u00fdm zmen\u00e1m (~ 1 %) a predstavuj\u00fa intermedi\u00e1rnu progn\u00f3zu. Doch\u00e1dza k nim v r\u00f4znych oblastiach, ale v\u0161etk\u00fdm pacientom \u00a0ch\u00fdba <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>g\u00e9n.<\/p>\n<p>K \u010fal\u0161\u00edm, zriedkavo detegovan\u00fdm \u00a0prestavb\u00e1m\u00a0 <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>g\u00e9nu, patria nebalansovan\u00e9 translok\u00e1cie, ad\u00edcie, duplik\u00e1cie, amplifik\u00e1cie, inverzie a inzercie (7).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>K<\/strong><strong>azui<\/strong><strong>s<\/strong><strong>t<\/strong><strong>ik<\/strong><strong>a<\/strong><\/p>\n<p>Predstavujeme zauj\u00edmav\u00fd pr\u00edpad mladej 34-ro\u010dnej pacientky, ktorej bola v j\u00fani 2014 stanoven\u00e1 diagn\u00f3za AML-M2 pod\u013ea FAB klasifik\u00e1cie. V \u010dase diagn\u00f3zy mala pacientka v KD pr\u00edtomn\u00fdch 85 % blastov a zo vzorky KD sme uskuto\u010dnili vstupn\u00e9 genetick\u00e9 vy\u0161etrenie.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>V<\/strong><strong>\u00fd<\/strong><strong>sl<\/strong><strong>e<\/strong><strong>d<\/strong><strong>k<\/strong><strong>y<\/strong><\/p>\n<p>Cytogenetick\u00e9 a FISH vy\u0161etrenie<\/p>\n<p>Cytogenetickou anal\u00fdzou metaf\u00e1z pripraven\u00fdch 24-hodinovou kultiv\u00e1ciou buniek KD sme odhalili drobn\u00fa translok\u00e1ciu t(11;17)(q23;q25) (obr\u00e1zok 1) a stanovili karyotyp 46,XX,t(11;17)(q23;q25). Translok\u00e1ciu sme potvrdili aj\u00a0pou\u017eit\u00edm celochromoz\u00f3mov\u00fdch \u00a0sond 11a 17 (obr\u00e1zok 2) a z\u00e1rove\u0148 sme pomocou fluorescen\u010dnej <em>i<\/em><em>n situ <\/em>hybridiz\u00e1cie (FISH) potvrdili aj prestavbu <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>g\u00e9nu v 88 % vy\u0161etren\u00fdch interf\u00e1zov\u00fdch jadr\u00e1ch za pou\u017eitia sondy XL MLL plus (Metasystems).<\/p>\n<p>Tri mesiace \u00a0po stanoven\u00ed diagn\u00f3zy (9\/2014) a dosiahnut\u00ed remisie podst\u00fapila pacientka nepr\u00edbuzensk\u00fa alog\u00e9nnu transplant\u00e1ciu krvotvorn\u00fdch buniek \u00a0(TKB). Darcom \u00a0bol mu\u017e, ktor\u00fd bol nosite\u013eom \u00a0fyziologickej pericentrickej inverzie chromoz\u00f3mu \u00a03 (obr\u00e1zok 3). Po\u010das nasleduj\u00faceho roka chodila pacientka na pravideln\u00e9 kontroln\u00e9 vy\u0161etrenia, ktor\u00e9 boli negat\u00edvne. A\u017e vy\u0161etrenie z janu\u00e1ra 2016 odhalilo relaps ochorenia \u00a0a k prim\u00e1rnej cytogenetickej zmene \u2013 translok\u00e1cii t(11;17)(q23;q25), pribudla sekund\u00e1rna zmena \u2013 del\u00e9cia dlh\u00e9ho ramena druh\u00e9ho chromoz\u00f3mu \u00a011-del(11)(q14)\u00a0(obr\u00e1zok 4). Sondou \u00a0XL MLL plus (Metasystems) \u00a0sme potvrdili pr\u00edtomnos\u0165 len jedn\u00e9ho <em>K<\/em><em>M<\/em><em>T2<\/em><em>A \u00a0<\/em>g\u00e9nu v prestavbe, druh\u00fd sign\u00e1l v d\u00f4sledku del\u00e9cie ch\u00fdbal (obr\u00e1zok 5). Posledn\u00e9 vy\u0161etrenia sme uskuto\u010dnili v marci 2016, ke\u010f sme na cytogenetickej \u00farovni detegovali len metaf\u00e1zy donora, av\u0161ak na FISH \u00farovni bola e\u0161te v 23 % pr\u00edtomn\u00e1 prestavba <em>K<\/em><em>M<\/em><em>T2<\/em><em>A\u00a0 <\/em>g\u00e9nu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Mol<\/strong><strong>e<\/strong><strong>k<\/strong><strong>ul<\/strong><strong>ov\u00e1 anal\u00fdza<\/strong><\/p>\n<p>Na molekulovej \u00farovni sme v \u010dase diagn\u00f3zy uskuto\u010dnili multiplexov\u00fa anal\u00fdzu PCR AMLplex (Mentype), ktor\u00e1 umo\u017e\u0148uje anal\u00fdzu 11 z\u00e1kladn\u00fdch f\u00faznych \u00a0transkriptov pri AML (<em>A<\/em><em>M<\/em><em>L<\/em><em>1<\/em><em>&#8211;<\/em><em>E<\/em><em>T<\/em><em>O, BCR-ABL, CALM-AF10, <\/em><em>C<\/em><em>B<\/em><em>F<\/em><em>B<\/em><em>&#8211; MYH11, DEK-CAN, MLL-AF6, MLL-AF9, MLL-PTD, NPM1-MLF1, PML-RARA<\/em>) s 31 transkrip\u010dn\u00fdmi variantmi. V\u00fdsledok bol negat\u00edvny, nebola dok\u00e1zan\u00e1 \u017eiadna zo spomenut\u00fdch translok\u00e1ci\u00ed. V \u010dase diagn\u00f3zy a po\u010das kontrol sa analyzoval aj <em>W<\/em> <em>T<\/em><em>1 <\/em>g\u00e9n, ktor\u00e9ho nadexpresia bola pozorovan\u00e1 u 90 % pacientov s AML. \u00a0V leukocytoch \u00a0kostnej drene zdrav \u00fdch jedincov sa hladina expresie <em>W<\/em> <em>T<\/em><em>1 <\/em>g\u00e9nu pohybuje r\u00e1dovo 10-2 NCN (normalizovan\u00fd po\u010det k\u00f3pi\u00ed ). V \u010dase diagn\u00f3zy a po\u010das relapsu sme vo vzork\u00e1ch KD pacientky zaznamenali zv\u00fd\u0161en\u00fa hladinu expresie <em>W<\/em><em>T<\/em><em>1 <\/em>g\u00e9nu, ktor\u00e1 koreluje s klinick\u00fdm priebehom \u00a0ochorenia \u00a0(8). V\u00fdsledky v\u0161etk\u00fdch \u00a0vy\u0161etren\u00ed \u00a0s\u00fa zhrnut\u00e9 v tabu\u013eke 1.<\/p>\n<p>&nbsp;<\/p>\n<p><em>Chim\u00e9rizmus \u2013 monitorovanie stavu krvotvorby po transplant\u00e1cii krvotvorn\u00fdch buniek<\/em><\/p>\n<p>Pacientka podst\u00fapila v septembri 2014 alog\u00e9nnu nepr\u00edbuzensk\u00fa transplant\u00e1ciu krvotvorn\u00fdch buniek a v s\u00fa\u010dasnosti je 611 dn\u00ed po transplan- t\u00e1cii. Chim\u00e9rizmus bol na molekulovej \u00farovni v pravideln\u00fdch intervaloch monitorovan\u00fd (Mentype). V 12\/2014 bola potvrden\u00e1 100 % krvotvorba darcu (kompletn\u00fd chim\u00e9rizmus). T\u00e1 v\u0161ak bola postupne, ako je uveden\u00e9 v grafe 1, vytl\u00e1\u010dan\u00e1 hematopo\u00e9zou \u00a0pacientky (zmie\u0161an\u00fd chim\u00e9rizmus). Percentu\u00e1lne zast\u00fapenia krvotvorby darcu a recipienta \u2013 pacientky, v kostnej dreni (KD) a perif\u00e9rnej krvi (PK) s\u00fa z druh\u00e9ho roku po transplant\u00e1cii.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Dis<\/strong><strong>k<\/strong><strong>usia<\/strong><\/p>\n<p>Pribli\u017ene 10 % v\u0161etk\u00fdch leuk\u00e9mi\u00ed a 3 \u2013 4 % v\u0161etk\u00fdch AML pr\u00edpadov m\u00e1 prestavbu <em>K<\/em><em>M<\/em><em>T2<\/em><em>A \u00a0<\/em>g\u00e9nu, ktor\u00e1 sa \u010dastej\u0161ie vyskytuje u mlad\u0161\u00edch pacientov s AML <em>de novo <\/em>ako u star\u0161\u00edch pacientov, \u010do sa potvrdilo aj u na\u0161ej pacientky \u00a0(3). Progn\u00f3za \u00a0pacientov \u00a0s translok\u00e1ciou \u00a0je r\u00f4zna, z\u00e1vis\u00ed od transloka\u010dn\u00e9ho partnera. Dodnes bolo klonovan\u00fdch a charakterizovan\u00fdch na molekulovej \u00farovni viac ako 70 r\u00f4znych partnersk\u00fdch g\u00e9nov a nov\u00e9 s\u00fa st\u00e1le objavovan\u00e9 a opisovan\u00e9 \u00a0(9). K naj\u010dastej\u0161ie vyskytuj\u00facim sa translok\u00e1ci\u00e1m patria t(11;19)(q23;p13), t(9;11)(22;q23) a t(10;11)(p12;q23). Translok\u00e1cie s lokusom 11q23 patria do nepriaznivej prognostickej skupiny okrem t(9;11)(p22;q23), ktor\u00e1 m\u00e1 signifikantne dlh\u0161ie pre\u017e\u00edvanie a sp\u00e1ja sa so strednou progn\u00f3zou. V na\u0161ej pr\u00e1ci opisujeme \u00a0zriedkav\u00fa translok\u00e1ciu t(11;17)(q23;q25) detegovan\u00fa na cytogenetickej \u00farovni v \u010dase diagn\u00f3zy. Translok\u00e1cie sa z\u00fa\u010dast\u0148uje z chromoz\u00f3mu \u00a011 g\u00e9n <em>K<\/em><em>M<\/em><em>T<\/em><em>2A <\/em>a z chromoz\u00f3mu\u00a017 pravdepodobne g\u00e9n <em>SE<\/em><em>PT9. <\/em>G\u00e9n <em>SE<\/em><em>PT9 <\/em>je \u010dlenom \u00a0sept\u00ednovej rodiny, ktor\u00fa tvor\u00ed 5 g\u00e9nov. Sept\u00edny s\u00fa GTP-via\u017euce \u00a0prote\u00edny a maj\u00fa d\u00f4le\u017eit\u00fa \u00falohu v procesoch bunkov\u00e9ho delenia a zachovania bunkovej integrity. Translok\u00e1cia t(11;17)(q23;q25) bola okrem pacientov s AML op\u00edsan\u00e1 aj u pacientov so sekund\u00e1rnou AML, ak\u00fatnou lymfoblastovou leuk\u00e9miou (ALL) a ve\u013emi zriedkavo u pacientov s myelodysplastick\u00fdm syndr\u00f3mom (MDS) a ako v\u00e4\u010d\u0161ina prestavieb s <em>K<\/em><em>M<\/em><em>T<\/em><em>2A <\/em>je spojen\u00e1 so zlou progn\u00f3zou (10). Chen et al. (11) vo svojej pr\u00e1ci uv\u00e1dzaj\u00fa ako naj\u010dastej\u0161ie sa vyskytuj\u00face sekund\u00e1rne aber\u00e1cie k prestavbe <em>K<\/em><em>M<\/em><em>T2<\/em><em>A\u00a0 <\/em>g\u00e9nu del\u00e9ciu chromoz\u00f3mov \u00a05,\u00a07, komplexn\u00fd \u00a0karyotyp a triz\u00f3miu chromoz\u00f3mu 8. Del\u00e9ciu \u00a0chromoz\u00f3mu\u00a011, ak\u00fa sme detegovali u na\u0161ej pacientky, nezaznamenali. Strata funkcie oboch g\u00e9nov <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>s\u00fa\u010dasne je ve\u013emi ojedinel\u00fd jav a zatia\u013e nie s\u00fa \u017eiadne liter\u00e1rne \u00fadaje o v\u00fdskyte a progn\u00f3ze.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Z<\/strong><strong>\u00e1<\/strong><strong>ver<\/strong><\/p>\n<p>Cytogenetick\u00e1 anal\u00fdza je nenahradite\u013enou s\u00fa\u010das\u0165ou vy\u0161etrovac\u00edch met\u00f3d v diagnostike hematologick\u00fdch malign\u00edt. Umo\u017e\u0148uje z\u00edska\u0165 celkov\u00fd karyotypov\u00fd obraz pacienta a odhali\u0165 aj r\u00f4zne \u0161trukt\u00farov\u00e9 a numerick\u00e9\u00a0aber\u00e1cie, ktor\u00e9 s\u00fa in\u00fdmi met\u00f3dami nedetegovate\u013en\u00e9. Umo\u017e\u0148uje ich sledova\u0165 v \u010dase diagn\u00f3zy, po\u010das lie\u010dby alebo relapsu. S FISH anal\u00fdzou a molekulovou met\u00f3dou sa navz\u00e1jom dop\u013a\u0148aj\u00fa, spolu umo\u017e\u0148uj\u00fa detegova\u0165 \u0161irok\u00e9 spektrum aber\u00e1ci\u00ed a maj\u00fa d\u00f4le\u017eit\u00fa \u00falohu v stanoven\u00ed progn\u00f3zy, klasifik\u00e1cii a mana\u017emente pacienta. Progn\u00f3za na\u0161ej pacientky je vzh\u013eadom na dan\u00fa translok\u00e1ciu a nepr\u00edtomnos\u0165 \u00a0ani jedn\u00e9ho \u00a0\u201ezdrav\u00e9ho\u201c a neporu\u0161en\u00e9ho <em>K<\/em><em>M<\/em><em>T2<\/em><em>A <\/em>g\u00e9nu ve\u013emi nepriazniv\u00e1. Pacientka \u00a0je v s\u00fa\u010dasnosti v zlom stave, rezistentn\u00e1 na chemoterapiu, \u00a0vo floridnej f\u00e1ze ochorenia.<\/p>\n<p><em>P<\/em><em>o\u010fa<\/em><em>k<\/em><em>ovanie: <\/em><em>\u010eakujem v\u0161etk\u00fdm kolegom, ktor\u00ed sa podie\u013eali <\/em><em>n<\/em><em>a pr\u00edprave a vy\u0161etrovan\u00ed vzoriek pacientky na cytogenetickej, FISH a molekulovej \u00farovni po\u010das uplynul\u00fdch dvoch rokov.<\/em><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Literat\u00fara<\/strong><br \/>\n1. Doubek M, Mayer J. Ak\u00fatn\u00ed myeloidn\u00ed leukemie. In: Posp\u00ed\u0161ilov\u00e1 \u0160, Dvo\u0159\u00e1kov\u00e1 D, Mayer J, et al. Molekul\u00e1rn\u00ed hematologie. Praha, Czech Republic: Gal\u00e9n; 2013: 209\u2013224.<\/p>\n<p>2. Yohe S. Molecular Genetic Markers in Acute Myeloid Leukemia. J Clin Med. 2015;460\u2013478.<\/p>\n<p>3. Ilencikova D, Kolenova A. MLL Gene Alterations in Acute Myeloid Leukaemia (11q23\/MLL+<br \/>\nAML), Oncogene and Cancer \u2013 From Bench to Clinic [online]. Dr. Yahwardiah Siregar, ed.<br \/>\nInTech. 2013. DOI: 10.5772\/55141. Available from: &lt;http:\/\/www.intechopen.com\/books\/oncogene-<br \/>\nand-cancer-from-bench-to-clinic\/mll-gene-alterations-in-acute-myeloid-leukaemia-<br \/>\n11q23-mll-aml&gt;.<\/p>\n<p>4. Launay E, Henry C, Meyer C, et al. MLL-SEPT5 fusion transcript in infant acute myeliod leukemia<br \/>\nwith t(11;22)(q23;q11). Leukemia &amp; Lymphoma. 2014;55(3):662\u2013667.<\/p>\n<p>5. Mejst\u0159\u00edkov\u00e1 S, Dvo\u0159\u00e1kov\u00e1 D. Ak\u00fatn\u00ed myeloidn\u00ed leuk\u00e9mie s abnormalitami genu MLL.<br \/>\nIn: Posp\u00ed\u0161ilov\u00e1 \u0160, Dvo\u0159\u00e1kov\u00e1 D, Mayer J, et al. Molekul\u00e1rn\u00ed hematologie. Praha, Czech Republic:<br \/>\nGal\u00e9n; 2013: 220.<\/p>\n<p>6. Saito H, Otsubo K, Kakimoto A, et al. Emergence of two unrelated clones in acute myeloid<br \/>\nleukemia with MLL-SEPT9 fusion transcript. Cancer Genet Cytogenet. 2010;201:111\u2013115.<\/p>\n<p>7. Zhao X, Li S, Li N, et al. 11q23 abnormalities in adult Chinese patients with hematological<br \/>\nmalignancies. Med Oncol. 2014;31:115.<\/p>\n<p>8. Ilen\u010d\u00edkov\u00e1 D, S\u00fdkora J, Mikul\u00e1\u0161ov\u00e1 Z, et al. Identifik\u00e1cia molekul\u00e1rnych markerov u det\u00ed<br \/>\ns ak\u00fatnou myeloblastovou leuk\u00e9miou (AML). Klin Onkol. 2015;25(1):26\u201335.<\/p>\n<p>9. Zhang Y, Chen A, Yan X-M, et a. Disordered epigenetic regulation in MLL-related leukemia.<br \/>\nInt J Hematol. 2012;96(4):428\u201337.<\/p>\n<p>10. Lee SG, Park TS, Seung HO, et al. De novo Acue Myeloid Leukemia Associated with t(11;17)<br \/>\n(q23;q25) and MLL-SEPT9 Rearrangement in an Elderly Patient: A Case Study and Review of<br \/>\nthe Literature. Acta Haematol. 2011;126:195\u2013198.<\/p>\n<p>11. Chen Y, Kantarjian H, Pierce S, et al. Prognostic significance of 11q23 aberrations in adult<br \/>\nacute myeloid leukemia and the role of allogeneic stem cell transplantation. Leukemia.<br \/>\n2013;27:836\u2013842.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. &nbsp; \u00davod Ak\u00fatne myeloidn\u00e9 leuk\u00e9mie (AML) predstavuj\u00fa heterog\u00e9nnu skupinu mal\u00edgnych ochoren\u00ed charakterizovan\u00fdch nekontrolovanou prolifer\u00e1ciou a akumul\u00e1ciou nezrel\u00fdch hematopoetick\u00fdch\u00a0 buniek v kostnej dreni (KD) a n\u00e1sledn\u00fdm vyplavovan\u00edm do perif\u00e9rnej krvi (PK).<\/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":[444,803,380,801,804,802],"class_list":["post-1182","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-aml-en","tag-cytogenetics","tag-fish-en","tag-kmt2-gene","tag-molecular-analysis","tag-translocation","typ_clanku-casuistry"],"acf":{"abstrakt":"<p><strong>Introduction:<\/strong> Acute myeloid leukemia (AML) is a phenotypically and genetically heterogenous clonal disease of blood-forming progenitor cells which causes rapid and uncontrolled proliferation of pathological cell population. Multiple structured and numeric AML-associated aberrations have been identified, many of which are predictors of clinical symptoms of the disease and therapeutic outcome. Reconstructions of the KMT2A gene localised in chromosome 11 in the q23 area belong among frequent findings.<\/p>\n<p><strong>Case study:<\/strong> In the presented case of a young patient with type M2 AML, we identified a rare t(11;17)(q23;q25) translocation during diagnosis by way of cytogenetic analysis.<\/p>\n<p><strong>Outcomes:<\/strong> Translocation was confirmed also by way of fluorescence <em>in situ <\/em>hybridisation (FISH) with chromosome probes. The patient later underwent extra-familiar allogenic transplant; a relapse occurred after 2 years and besides the primary aberration, a secondary aberration occurred \u2013 deletion of the long arm of the second chromosome 11.<\/p>\n<p><strong>Discussion:<\/strong> Prognosis of patients with reconstruction of the <em>KMT2 <\/em>gene differs; it depends on the translocation partner. Translocation t(11;17)(q23;q25) is associated with poor prognosis. Literature describes various secondary aberrations, however deletion of the second chromosome 11 and therefore absence of functional <em>KMT2 <\/em>gene has not been described.<\/p>\n<p><strong>Conclusion:<\/strong> Cytogenetic analysis plays and important role in diagnosis of hematological malignity. In combination with FISH analysis and molecular method, the methodologies are complementary and enable detection of a wider range of aberrations and play an important role in establishing prognosis, classification and patient management.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Key words: <\/strong>AML, <em>KMT2 <\/em>gene, translocation, cytogenetics, FISH, molecular analysis<\/p>\n<p>&nbsp;<\/p>\n","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"<ul>\r\n \t<li>Pulmonary aspergillosis<\/li>\r\n \t<li>Infections caused by cytomegalovirus \u2013 diagnosis and therapy<\/li>\r\n \t<li>Long-term molecular remission as a precondition for successful pregnancy in patients with chronic myelocyte leukemia<\/li>\r\n \t<li>Chromosome 11 aberrations in a patient with acute myeloid leukemia \u2013 a case study<\/li>\r\n \t<li>New biomarkers in diagnosing IgA nephropathy<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2016-02","to_ping":"","pinged":"","post_modified":"2017-08-16 21:36:48","post_modified_gmt":"2017-08-16 19:36:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2016-02\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"117","upload_clanok":{"ID":1183,"id":1183,"title":"Newslab_2_2016_Aber\u00e1cie chromoz\u00f3mu 11 u pacientky s ak\u00fatnou","filename":"Newslab_2_2016_Aber\u00e1cie-chromoz\u00f3mu-11-u-pacientky-s-ak\u00fatnou.pdf","filesize":223448,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/01\/Newslab_2_2016_Aber\u00e1cie-chromoz\u00f3mu-11-u-pacientky-s-ak\u00fatnou.pdf","link":"https:\/\/www.newslab.sk\/en\/chromosome-11-aberrations-in-a-patient-with-acute-myeloid-leukemia-a-case-study\/newslab_2_2016_aberacie-chromozomu-11-u-pacientky-s-akutnou\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2_2016_aberacie-chromozomu-11-u-pacientky-s-akutnou","status":"inherit","uploaded_to":1182,"date":"2017-02-01 19:29:08","modified":"2017-02-01 19:29:08","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\/1182","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=1182"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1182\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1182"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1182"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1182"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}