{"id":1944,"date":"2020-05-05T15:59:22","date_gmt":"2020-05-05T13:59:22","guid":{"rendered":"https:\/\/www.newslab.sk\/homogenne-sa-farbiace-oblasti-u-pacientov-s-leukemiou-kazuistiky\/"},"modified":"2020-05-05T16:14:40","modified_gmt":"2020-05-05T14:14:40","slug":"homogenne-sa-farbiace-oblasti-u-pacientov-s-leukemiou-kazuistiky","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/homogenne-sa-farbiace-oblasti-u-pacientov-s-leukemiou-kazuistiky\/","title":{"rendered":"The homogeneously staining regions in patients with leukaemia (case reports)"},"content":{"rendered":"

*<\/strong>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

 <\/p>\n

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

Leuk\u00e9mia je mal\u00edgne ochorenie krvotvorn\u00fdch buniek, pri ktorom doch\u00e1dza k zmno\u017eeniu a hromadeniu nezrel\u00fdch foriem bielych krviniek a tie postupne obsadzuj\u00fa priestory v kostnej dreni a potl\u00e1\u010daj\u00fa norm\u00e1lnu krvotvorbu. S leuk\u00e9miou sa sp\u00e1jaj\u00fa r\u00f4zne \u0161trukt\u00farne chromoz\u00f3mov\u00e9 zmeny, ako s\u00fa translok\u00e1cie, del\u00e9cie, inverzie, ad\u00edcie, alebo numerick\u00e9 zmeny, ako s\u00fa aneuploidie, polyploidie chromoz\u00f3mov(1). Zriedkavo sa v\u0161ak (~ 1 %) stret\u00e1vame s cytogeneticky vidite\u013en\u00fdm znakom amplifik\u00e1cie DNA. Toto mnohon\u00e1sobn\u00e9 zmno\u017eenie DNA sa m\u00f4\u017ee vyskytova\u0165 extrachromoz\u00f3movo ako tzv. double minute (dmin), mal\u00e9 p\u00e1rov\u00e9 chromat\u00ednov\u00e9 telieska bez centrom\u00e9ry alebo intrachromoz\u00f3movo, zn\u00e1me ako homog\u00e9nne sa farbiace oblasti (hsrhomogenously staining region), ke\u010f je zmno\u017eenie integrovan\u00e9 do chromoz\u00f3mu (obr\u00e1- zok 1)<\/em><\/strong>. Mechanizmus vzniku nie je \u00faplne objasnen\u00fd. Prv\u00fdkr\u00e1t boli op\u00edsan\u00e9 v roku 1962 u pacientov s bronchog\u00e9nnym karcin\u00f3mom(2). N\u00e1sledkom amplifik\u00e1cie DNA doch\u00e1dza k zv\u00fd\u0161enej expresii g\u00e9nov obsiahnut\u00fdch v amplik\u00f3ne, doch\u00e1dza\u00a0 k modifik\u00e1cii norm\u00e1lneho bunkov\u00e9ho delenia a pre\u017e\u00edvania buniek. Zmno\u017eenie m\u00e1 potenci\u00e1lny leukemog\u00e9nny \u00fa\u010dinok\u00a0 a je asociovan\u00e9 s r\u00fdchlou progresiou ochorenia a kr\u00e1tkym \u010dasom pre\u017e\u00edvania. Naj\u010dastej\u0161ie amplifikovan\u00fdmi g\u00e9nmi s\u00fa MYC, MYCN <\/em>(neuroblast\u00f3m), HER2\/neu <\/em>(n\u00e1dory prsn\u00edka), KMT2A<\/em>(3).<\/p>\n

 <\/p>\n

Materi\u00e1l a met\u00f3dy<\/h3>\n

V \u010dl\u00e1nku predstavujeme troch pacientov, u ktor\u00fdch sme cytogenetickou anal\u00fdzou detegovali homog\u00e9nne sa farbiace oblasti a pomocou FISH met\u00f3dy sme odhalili ich p\u00f4vod.<\/p>\n

Na cytogenetick\u00fa anal\u00fdzu boli pou\u017eit\u00e9 vzorky kostnej drene kultivovan\u00e9 24 hod\u00edn v kompletnom kultiva\u010dnom m\u00e9diu pri 37 \u00b0C a n\u00e1sledne spracovan\u00e9 pod\u013ea \u0161tandardn\u00fdch cytogenetick\u00fdch postupov. Prepar\u00e1ty boli farben\u00e9 Wrightov\u00fdm roztokom a u ka\u017ed\u00e9ho pacienta bolo hodnoten\u00fdch 20 G-pr\u00fa\u017ekovan\u00fdch metaf\u00e1z. Karyotyp bol zap\u00edsan\u00fd pod\u013ea International System of Chromosome Nomenclature (ISCN)(4).<\/p>\n

Na FISH anal\u00fdzu boli pou\u017eit\u00e9 suspenzie pripraven\u00e9 spomenut\u00fdm postupom. Boli pou\u017eit\u00e9 nasledovn\u00e9 sondy od firmy Metasystems XL Del(5)(q31), XL 7q22\/7q36, XL TP53\/ 17cen, XCE 8 Blue, XL 22q11 IGL BA, XL 20q12\/20qter, XL Iso(17q), XCE 12 Orange, XL MLL plus, sonda ZytoLight<\/em>\u00ae <\/strong>SPEC BCL2 DC BA od Zytovision a sonda LSI 21 SO od firmy Abbott. Prepar\u00e1ty a sondy boli denaturovan\u00e9, n\u00e1sledne prebehla hybridiz\u00e1cia a hodnotenie 200 interf\u00e1zov\u00fdch jadier pod fluorescen\u010dn\u00fdm mikroskopom.<\/p>\n

Na molekulovej \u00farovni sa u pacientov po izol\u00e1cii DNA z kostnej drene alebo perif\u00e9rnej krvi realizovala MLPA anal\u00fdza pomocou kitu MDS P414-A1. Technika deteguje len numerick\u00e9 zmeny, del\u00e9cie a amplifik\u00e1cie. Obsahuje 46 sond pre nieko\u013eko chromoz\u00f3mov, ktor\u00e9 maj\u00fa diagnostick\u00fd alebo prognostick\u00fd v\u00fdznam pre pacientov s myelodysplastick\u00fdm syndr\u00f3mom (MDS) (chromoz\u00f3my 3, 5q, 7q, 8q, 11q, 12p, 17, 19, 20q, Y).<\/p>\n

 <\/p>\n

Kazuistika \u010d. 1<\/h3>\n

V j\u00fani 2016 sme na na\u0161e oddelenie prijali vzorku kostnej drene 78-ro\u010dnej pacientky s diagn\u00f3zou ak\u00fatna myeloblastov\u00e1 leuk\u00e9mia (AML) bli\u017e\u0161ie neur\u010den\u00e9ho typu. Na cytogenetickej \u00farovni sme analyzovali 20 G-bandovan\u00fdch metaf\u00e1z a stanovili sme komplexn\u00fd karyotyp (obr\u00e1zok 2)<\/em><\/strong>: <\/strong>47,XX,-der(5)t(5;21)(p11;q21),-17,+21,der(22)t(17;22)(q21;q10), +hsr(22)(q11)[20].<\/p>\n

Na prepar\u00e1toch sme uskuto\u010dnili aj FISH anal\u00fdzu pomocou sond pou\u017e\u00edvan\u00fdch pri diagn\u00f3ze MDS a zachytili sme zmeny zhrnut\u00e9 v tabu\u013eke 1<\/em><\/strong>.<\/p>\n

Vy\u0161etrenie IGL <\/em>g\u00e9nu lokalizovan\u00e9ho na chromoz\u00f3me 22 bolo uskuto\u010dnen\u00e9 pomocou sondy XL IGL BA z Metasystems (obr\u00e1zok<\/em><\/strong> 3)<\/em><\/strong>. Detegovali sme amplifik\u00e1ciu len zelenej 3\u00b4oblasti (obr\u00e1zok<\/em><\/strong> 4)<\/em><\/strong>, v ktorej sa nach\u00e1dza g\u00e9n BCR<\/em>. Napriek tomu, \u017ee f\u00fazny prote\u00edn bcr\/abl patr\u00ed k ve\u013emi sk\u00faman\u00fdm, nie je funkcia norm\u00e1lneho BCR <\/em>g\u00e9nu \u00faplne objasnen\u00e1. Predpoklad\u00e1 sa, \u017ee m\u00e1 GTP-\u00e1zov\u00fa aktivitu a reguluje sign\u00e1lne dr\u00e1hy v bunke(5). Z\u00e1rove\u0148 sme pacientke detegovali stratu centrom\u00e9ry a kr\u00e1tkych ramien chromoz\u00f3mu 17, na ktor\u00fdch je lokalizovan\u00fd tumorsupresorov\u00fd g\u00e9n TP53<\/em>. B\u00fdva tie\u017e ozna\u010dovan\u00fd ako str\u00e1\u017eca gen\u00f3mu. Jeho \u00falohou je udr\u017eova\u0165 gen\u00f3mov\u00fa stabilitu a integritu, regulova\u0165 expresiu mnoh\u00fdch g\u00e9nov s d\u00f4le\u017eitou \u00falohou pri bunkovom raste, delen\u00ed, apopt\u00f3ze, angiogen\u00e9ze a m\u00e1 k\u013e\u00fa\u010dov\u00fa \u00falohu v ochrane pred tvorbou n\u00e1doru (6,7). MLPA anal\u00fdza potvrdila amplifik\u00e1ciu 22q11.21, del\u00e9ciu 5q22-q34, 17p13.1, 17q11.2 a odhalila del\u00e9ciu kr\u00e1tkych ramien chromoz\u00f3mu 3 (3p22.2) (obr\u00e1zok<\/em><\/strong> 5)<\/em><\/strong>. Pacientka exitovala e\u0161te toho mesiaca.<\/p>\n

 <\/p>\n

Kazuistika \u010d. 2<\/h3>\n

V apr\u00edli 2017 sme na na\u0161e oddelenie prv\u00fdkr\u00e1t prijali vzorku perif\u00e9rnej krvi 73-ro\u010dn\u00e9ho pacienta s diagn\u00f3zou myelo- dysplastick\u00fd syndr\u00f3m (MDS). Na molekulovej \u00farovni bola realizovan\u00e1 MLPA anal\u00fdza, ktor\u00e1 preuk\u00e1zala pr\u00edtomnos\u0165 amplifik\u00e1cie chromoz\u00f3mu 11 v oblasti q23.3-q24.3. O mesiac nesk\u00f4r, v m\u00e1ji, sme prijali vzorku kostnej drene a vy\u0161etrenie bolo doplnen\u00e9 o cytogenetiku a FISH anal\u00fdzu. Po cytogenetickej anal\u00fdze sme v 13 metaf\u00e1zach identifikovali komplexn\u00fd karyotyp s marker chromoz\u00f3mom (obr\u00e1zok 6)<\/em><\/strong>: 45,XY,-5,der(11)t(5;11)(p13;q22),+hsr(11)(q23),der(12)t(11;12,?)(q23;q11;?),-18[6]\/46,idem,+22[7]\/46,XY[7]. V\u00fdsledky FISH anal\u00fdz s\u00fa uveden\u00e9 v tabu\u013eke 2<\/em><\/strong>.<\/p>\n

Pomocou sondy MLL plus dc (obr\u00e1zok 7) <\/em><\/strong>sme odhalili, \u017ee marker chromoz\u00f3m je cel\u00fd tvoren\u00fd namno\u017een\u00fdm g\u00e9nom KM- T2A <\/em>(star\u0161\u00ed n\u00e1zov MLL<\/em>) a z\u00e1rove\u0148 na chromoz\u00f3me 11 sa tie\u017e vyskytuje KMT2A <\/em>g\u00e9n dvakr\u00e1t za sebou (obr\u00e1zok 8)<\/em><\/strong>. KMT2A <\/em>g\u00e9n k\u00f3duje transkrip\u010dn\u00fd koaktiv\u00e1tor, ktor\u00fd m\u00e1 d\u00f4le\u017eit\u00fa \u00falohu v regul\u00e1cii g\u00e9novej expresie po\u010das v\u010dasn\u00e9ho v\u00fdvoja a hematopo\u00e9zy(8).<\/p>\n

Na obr\u00e1zku 9 <\/em><\/strong>je odhalen\u00e1 del\u00e9cia oblasti 5q31, ktor\u00e1 sp\u00f4sobuje, \u017ee nezrel\u00e9 krvn\u00e9 bunky nie s\u00fa schopn\u00e9 dodiferencova\u0165 sa norm\u00e1lne a v\u00fdsledkom je ve\u013ea nezrel\u00fdch foriem buniek a m\u00e1lo zrel\u00fdch. Naj\u010dastej\u0161ie deletovan\u00fd regi\u00f3n DNA obsahuje 40 g\u00e9nov.<\/p>\n

Na obr\u00e1zku 10 <\/em><\/strong>je potvrden\u00e1 triz\u00f3mia chromoz\u00f3mu 22 pomocou FISH met\u00f3dy. Pacient koncom j\u00fana 2017 exitoval.<\/p>\n

Kazuistika \u010d. 3<\/h3>\n

Vzorka kostnej drene 68-ro\u010dn\u00e9ho pacienta bola v na\u0161om laborat\u00f3riu prv\u00fdkr\u00e1t vy\u0161etren\u00e1 v janu\u00e1ri 2017. Diagn\u00f3za bola myelodysplastick\u00fd syndr\u00f3m. V 10-tich metaf\u00e1zach sme ur\u010dili nasledovn\u00fd komplexn\u00fd karyotyp (obr\u00e1zok 11)<\/em><\/strong>: 47,XY,del(5)(q15q33),der(7)del(7)(q11)t(3;7)(q13;q11), +hsr(21)(q22)[10]\/46,XY[10]. Vy\u0161etrenie kostnej drene bolo doplnen\u00e9 o FISH anal\u00fdzu a v\u00fdsledky s\u00fa zhrnut\u00e9 v tabu\u013eke 3<\/em><\/strong>. V oblasti 21q22, ktor\u00e1 bola vy\u0161etren\u00e1 sondou LSI 21 SO (obr\u00e1zok 12) <\/em><\/strong>a bola detegovan\u00e1 amplifik\u00e1cia (obr\u00e1zok 13)<\/em><\/strong>, sa nach\u00e1dza g\u00e9n RUNX1 <\/em>(star\u0161\u00ed n\u00e1zov AML1<\/em>). Tento g\u00e9n k\u00f3duje transkrip\u010dn\u00fd faktor zodpovedn\u00fd za regul\u00e1ciu diferenci\u00e1cie hematopoetick\u00fdch buniek na zrel\u00e9 bunky(9). Pomocou sondy XL 7q22\/7q36 bola potvrden\u00e1 strata dlh\u00fdch ramien chromoz\u00f3mu 7, ke\u010f ostali v karyotype len kr\u00e1tke ramen\u00e1 a centrom\u00e9ra chromoz\u00f3mu 7 (modr\u00e1 farba, obr\u00e1zok 14<\/em><\/strong>). MLPA anal\u00fdza potvrdila del\u00e9ciu 5q22.2-q33.1 a 7q22.3-q36.1 a odhalila del\u00e9ciu 3p22.2, nezachyten\u00fa na cytogene- tickej \u00farovni.<\/p>\n

Pacient v marci 2017 exitoval.<\/p>\n

 <\/p>\n

Diskusia<\/h3>\n

Homog\u00e9nne sa farbiace oblasti s\u00fa chromoz\u00f3mov\u00e9 miesta s mnohon\u00e1sobn\u00fdm opakovan\u00edm (~20 \u2013 100) segmentov DNA. S\u00fa charakteristick\u00fdm znakom mal\u00edgneho procesu a zvy\u010dajne s\u00fa detegovan\u00e9 v pokro\u010dil\u00fdch \u0161t\u00e1di\u00e1ch mal\u00edgneho procesu spojen\u00e9 so zlou progn\u00f3zou. N\u00e1sledkom zmno\u017eenia sa m\u00f4\u017eu vytv\u00e1ra\u0165 r\u00f4zne ve\u013ek\u00e9 markery vyskytuj\u00face sa samostatne alebo sa m\u00f4\u017eu v\u010dleni\u0165 do chromoz\u00f3mu. Ke\u010f\u017ee sa farbia rovnomerne, ich identifik\u00e1cia pomocou G-bandu je ve\u013emi n\u00e1ro\u010dn\u00e1. Na odhalenie p\u00f4vodu zmno\u017eenia sa preto naj\u010dastej\u0161ie vyu\u017e\u00edva FISH met\u00f3da.<\/p>\n

Hoci boli op\u00edsan\u00e9 amplifik\u00e1cie r\u00f4znych g\u00e9nov, naj\u010dastej\u0161ie amplifikovan\u00e9 s\u00fa g\u00e9ny z malej g\u00e9novej rodiny MYC <\/em>(MYC<\/em>, MYCN<\/em>, and MYCL<\/em>). S\u00fa identifikovan\u00e9 v mnoh\u00fdch sol\u00eddnych n\u00e1doroch, ako s\u00fa n\u00e1dory mozgu, prsn\u00edka, pankreasu, neuroblast\u00f3m. V hematologick\u00fdch malignit\u00e1ch sa vyskytuj\u00fa zriedka, okolo 1 %(10). Tu \u010dasto amplifikovan\u00fdm g\u00e9nom b\u00fdva KM- T2A<\/em>, ktor\u00e9ho amplifik\u00e1ciu sme detegovali u n\u00e1\u0161ho jedn\u00e9ho pacienta. KMT2A <\/em>g\u00e9n je lokalizovan\u00fd v lokuse 11q23 a v leuk\u00e9mi\u00e1ch sa vyskytuje hlavne v translok\u00e1ci\u00e1ch, doteraz bolo identifikovan\u00fdch viac ako 80 jeho f\u00faznych partnerov(11).<\/p>\n

Pacienti s amplifik\u00e1ciou 11q23 sa vyskytuj\u00fa pomerne zriedkavo, maj\u00fa v\u0161ak niektor\u00e9 \u010drty ve\u013emi podobn\u00e9: s\u00fa to pacienti star\u0161ieho veku, s de novo ochoren\u00edm AML\/MDS, s komplexn\u00fdm karyotypom a kr\u00e1tkym pre\u017e\u00edvan\u00edm. U 90 % pacientov je tie\u017e pr\u00edtomn\u00e1 del\u00e9cia dlh\u00fdch ramien chromoz\u00f3mu 5, ktorej ve\u013ekos\u0165 var\u00edruje, ale v\u0161etk\u00fdm pacientom ch\u00fdba oblas\u0165 5q31(12).<\/p>\n

Druh\u00fdm najmen\u0161\u00edm chromoz\u00f3mom v karyotype, ktor\u00fd obsahuje ~ 600 g\u00e9nov, je chromoz\u00f3m 22. Pomocou FISH met\u00f3dy sme detegovali amplifik\u00e1ciu jeho 3\u00b4oblasti q11, v ktorej sa nach\u00e1dzaj\u00fa g\u00e9ny IGLC <\/em>a BCR<\/em>. IGLC <\/em>k\u00f3duje imunoglobul\u00ednov\u00fd lambda re\u0165azec, ktor\u00e9ho prestavba je pr\u00edtomn\u00e1 hlavne v lymf\u00f3moch. Pri hematologick\u00fdch malignit\u00e1ch je amplifik\u00e1cia g\u00e9nu BCR <\/em>zriedkav\u00e1, naj\u010dastej\u0161ie je g\u00e9n opisovan\u00fd v translok\u00e1cii t(9;22)(q34;q11), na molekulovej \u00farovni f\u00fazia bcr\/abl.<\/p>\n

Obr\u00e1zok 13. <\/em><\/strong>FISH anal\u00fdza pomocou sondy LSI 21 SO zn\u00e1zor\u0148u<\/em>j\u00faca amplifik\u00e1ciu 21q22<\/em><\/p>\n

Obr\u00e1zok 14. <\/em><\/strong>FISH vy\u0161etrenie pomocou sondy XL 7q22\/7q36, \u0161\u00edp<\/em>kou je zn\u00e1zornen\u00fd deletovan\u00fd chromoz\u00f3m<\/em><\/p>\n

G\u00e9n BCR <\/em>k\u00f3duje prote\u00edn so ser\u00edn\/treon\u00ednkin\u00e1zovou aktivitou zahrnut\u00fd v sign\u00e1lnej transdukcii, jeho presn\u00e1 \u00faloha v\u0161ak nie je odhalen\u00e1(5).<\/p>\n

Tret\u00edm chromoz\u00f3mom, na ktorom sme potvrdili amplifik\u00e1ciu, bol chromoz\u00f3m 21. Pou\u017eit\u00e1 sonda LSI 21 SO hybridizuje k oblasti 21q22. Ktor\u00fd g\u00e9n z danej oblasti je presne amplifikovan\u00fd, nevieme, ale kandid\u00e1tnym g\u00e9nom je g\u00e9n RUNX1 <\/em>(21q22.1). RUNX1 <\/em>g\u00e9n zohr\u00e1va v\u00fdznamn\u00fa \u00falohu pri hematopoetickej diferenci\u00e1cii a v mnoh\u00fdch in\u00fdch bunkov\u00fdch funkci\u00e1ch. Patr\u00ed ku g\u00e9nom, ktor\u00e9 s\u00fa pri leuk\u00e9mi\u00e1ch \u010dast\u00fdm cie\u013eov\u00fdm miestom translok\u00e1ci\u00ed. S amplifik\u00e1ciou g\u00e9nu RUNX1 <\/em>sa stret\u00e1vame hlavne pri detsk\u00fdch ak\u00fatnych leuk\u00e9mi\u00e1ch, no m\u00f4\u017ee sa vyskytova\u0165 aj u dospel\u00fdch s komplexn\u00fdm karyotypom a je spojen\u00e1 so zlou progn\u00f3zou(13,14).<\/p>\n

 <\/p>\n

Z\u00e1ver<\/h3>\n

Hsr\/dm sa vyskytuj\u00fa preva\u017ene u star\u0161\u00edch pacientov s diagn\u00f3zou AML alebo MDS. U pacientov je pr\u00edtomn\u00fd komplexn\u00fd karyotyp s del\u00e9ciou dlh\u00fdch ramien 5. chromoz\u00f3mu so spolo\u010dnou deletovanou oblas\u0165ou 5q31. S komplexn\u00fdmi zmenami sa tie\u017e sp\u00e1ja strata g\u00e9nu TP53 <\/em>z chromoz\u00f3mu 17. Pacienti s hsr\/dm maj\u00fa zl\u00fa progn\u00f3zu a kr\u00e1tke pre\u017e\u00edvanie, \u010do sa potvrdilo u v\u0161etk\u00fdch nami prezentovan\u00fdch pacientov.<\/p>\n

 <\/p>\n

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

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  12. Herry A, Douet-Guilbert N, Gu\u00e9ganic N, et Del(5q) and MLL amplification in homogeneously staining region in acute myeloblastic leukemia: a recurrent cytogenetic association. Annals of Hematology 2006; 85: 244-249.<\/li>\n
  13. Baldus C, Liyanarachchi S, Mr\u00f3zek K, et al. Acute myeloid leukemia with complex karyotype and abnormal chrosomome 21: Amplification discloses overexpression of APP, ETS2 and REG genes. PNAS 2004; 101(11): 3915-3920.<\/li>\n
  14. Mikhail FM, Sinha KK, Saunthararajah Y, et Normal and transforming functions of RUNX1: A perspective. Journal of cellular Physiology 2006; 207(3): 582-593.<\/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 Leuk\u00e9mia je mal\u00edgne ochorenie krvotvorn\u00fdch buniek, pri ktorom doch\u00e1dza k zmno\u017eeniu a hromadeniu nezrel\u00fdch foriem bielych krviniek a tie postupne obsadzuj\u00fa priestory v kostnej dreni a potl\u00e1\u010daj\u00fa norm\u00e1lnu<\/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":[1409,1408,380,1407],"class_list":["post-1944","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-complex-karyotype","tag-cytogenetic-analysis","tag-fish-en","tag-homogeneously-staining-regions","typ_clanku-casuistry"],"acf":{"abstrakt":"

    Introduction: <\/strong>The homogeneously staining regions (hsr) just as the dmin represent cytogenetically visible signs of gene amplification. They contain copies of an amplified DNA segment. Although found in the variety of human cancer cells, their presence in hematologic malignancies is rare. Their role in leukemogenesis is not clear, but they have been reported to be associated with rapid progression and short survival time. The mechanism of their origination is not known exactly. Characteristically, hsr can be detected after chromosome banding in metaphase preparations as a large chunk of diffusely staining chromatin somewhere inside an ordinary chromosome. Case reports: <\/strong>We report three patients with de novo AML and MDS who were examined by the cytogenetic analysis, FISH and MLPA method in our laboratory at the time of diagnosis. After 24-hour cultivation of bone marrow cells, the analysis of G-banded chromosomes revealed complex karyotype including deletion of the long arm of chromosome 5, the presence of hsr and other numerical and structural changes. The use of FISH method enabled the identification of chromosome aberrations and genes amplified in hsr and the determination of their percentage.<\/p>\n

    Results: <\/strong>All three patients shared the same characteristics: they were old, de-novo <\/em>diagnosis AML or MDS with complex karyotype including deletion of 5q, bad prognosis and short survival time.<\/p>\n

    Keywords: <\/strong>homogeneously staining regions, cytogenetic analysis, FISH, complex karyotype<\/p>\n","casopis":[{"ID":1893,"post_author":"7","post_date":"2020-05-05 11:32:54","post_date_gmt":"2020-05-05 09:32:54","post_content":"

      \r\n \t
    • Identification of metabolic pathways in pathogenesis of diabetic retinopathy using exome sequencing \u2013 a pilot study<\/li>\r\n \t
    • Anti-tumour effects of vitamin D<\/li>\r\n \t
    • Molecular detection methods of mutations in the kinase domain of fusion gene bcr-abl1 in patients with chronic myelocyte leukemia<\/li>\r\n \t
    • The case report of toxoplasmic meningoencephalitis with fatal outcome in HIV patient<\/li>\r\n \t
    • Carcinosarcoma-like endometrioid carcinoma of the uterus: case report of rare non-high-grade tumor<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-4","to_ping":"","pinged":"","post_modified":"2020-05-05 15:13:41","post_modified_gmt":"2020-05-05 13:13:41","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/?post_type=casopis&p=1893","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"63-68","upload_clanok":{"ID":1933,"id":1933,"title":"NEWSLAB_1-2020_Blahov\u00e1","filename":"NEWSLAB_1-2020_Blahov\u00e1.pdf","filesize":475251,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2020\/05\/NEWSLAB_1-2020_Blahov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/homogenne-sa-farbiace-oblasti-u-pacientov-s-leukemiou-kazuistiky\/newslab_1-2020_blahova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab_1-2020_blahova-2","status":"inherit","uploaded_to":1944,"date":"2020-05-05 13:46:50","modified":"2020-05-05 13:46:50","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\/1944","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=1944"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1944\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1944"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1944"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1944"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}