Ngokusekelwe kuGene Study, i-AML Leukemia inezinhlamvu ezingu-11

I-leukemia ayiyona isifo esisodwa, kodwa iningi. Ososayensi baqala ukuqonda ukuthi ngisho noma uhlobo olulodwa olulodwa lwe-leukemia lunezinhlayiyana ezihlukene ngezindlela ezibalulekile.

Izinhlobo ezine eziyinhloko ze-leukemia zincike ekutheni ziyi-leukemia enesifo esiphuthumayo noma engapheliyo, futhi lezi zigaba eziyinhloko zilandelayo:

Mayelana ne-AML

I-leukemia evamile ye-myelogenous ingumdlavuza we- bone lomnkantsha-ama -spiny insides amathambo, lapho amangqamuzana egazi enza khona-futhi futhi umdlavuza wegazi.

I-AML ibhekwa njenge-"acute" leukemia ngoba iqhubekela phambili ngokushesha. Ingxenye ye-myelogenous yegama ivela kumaseli-myeloid-iqoqo lamaseli ngokuvamile evame ukuba yizinhlobonhlobo zamaseli egazi avuthiwe, njengezibomvu zegazi elibomvu, amaseli egazi amhlophe namaplatelet.

I-AML inezixazululo eziningi: I-leukemia evamile ye-myelogenous iyaziwa nangokuthi i-lemonemic acute myeloid, i-myeloblastic leukemia, i-leukemia ejulile ye-granulocytic kanye ne-acute leyemia ye-nonlymphocytic.

I-AML ingathinta abantu bazo zonke ubudala. Umkhankaso we-World Health Organization ka-2012 we-GLOBOCAN uphakamise ukuthi abantu abangaba ngu-352,000 emhlabeni wonke babe ne-AML, futhi lesi sifo siba seminyaka eminingi kakhulu.

Izimpawu nezimpawu ze-AML zihlanganisa:

Ama-subtypes

Ukuhlelwa kwe-AML okusekelwe ekubukeni ezincane zamangqamuzana omdlavuza, noma i-morphology, kwandiswa yizinto ezintsha ezitholakalayo mayelana nezinguquko zofuzo noma izinguquko ezithintekayo ezifweni ezihlukahlukene zalesi sifo.

Abacwaningi e-Wellcome Trust Sanger Institute nabahlanganyeli abasanda kufaka esiteshini solwazi, ukubika ngokushintshashintsha kwezakhi zofuzo okusiza ukujula ukuqonda kwe-AML-okuqhubekayo kushintshe umqondo we-AML kusuka kwesifo esisodwa kuya kokunye okungenani izinhlobo ezingu-11 ezihlukahlukene zofuzo ukuhlukumezeka , ngokungafani okungasiza ekuchazeni izikhathi zokuphila ezihlukahlukene phakathi kweziguli ezincane ezine-AML.

Abacwaningi bashicilela isifundo sabo kwi-genetics ye-AML kumagazini ka-June 2016 we-"New England Journal of Medicine," futhi ochwepheshe bakholelwa ukuthi lezi zithole zingathuthukisa izilingo zokwelashwa futhi zithinte indlela iziguli ezine-AML ezifunyanwa futhi ziphathwe ngayo esikhathini esizayo.

Isifundo se-NEJM

Abacwaningi bacwaninga iziguli ezingu-1,540 ezine-AML ababhalisile ekuvivinyweni kwemitholampilo. Bahlaziya izakhi zofuzo ezingaphezu kuka-100 ezaziwa ukuthi zibangelwa i-leukemia ngenhloso yokukhomba "izihloko zofuzo" ngemuva kokuthuthukiswa kwesifo.

Bathole ukuthi iziguli ezine-AML zingahlukana zibe amaqembu amakhulu ama-11, ngayinye enezinhlobonhlobo zezinguquko zofuzo kanye nezici nezici ezihlukile. Ngokusho kocwaningo, iziguli eziningi zinezinhlanganisela eziyingqayizivele zokuguqula izakhi zofuzo ezihambisa i-leukemia, ezingasiza ukuchaza ukuthi kungani i-AML ibonisa ukwehluka okunjalo kumanani okusinda.

Imiphumela

Ukwazi ukukhiqizwa kwesifo se-leukemia yesiguli kungathuthukisa ikhono lokubikezela ukuthi ngabe izindlela zokwelashwa zamanje zizophumelela yini. Ulwazi lwalolu hlobo lungasetshenziswa ukuklama ukuhlolwa okusha kwemitholampilo ukuthuthukisa ukwelashwa okungcono kakhulu kwe-AML subtype ngayinye; futhi ekugcineni, ukuhlolwa okubanzi kwezakhi zofuzo ze-AML ekuxilongweni kungaba isimiso esiningi.

Kuhlelo lukaHulumeni lwe-World Health Organization (WHO) lwe-2008, ososayensi sebevele baqala ukuhlukanisa ama-AML abantu abadala "emaqenjini ama-molecule" ahlukile, kuhlanganise nezinguquko ezithile zofuzo noma ukulimala kwama-chromosomes okuchazwe kanje: t (15; 17), t (8; 21) ), inv (16) -t (16; 16), t (6; 9), inv (3) -t (3; 3), izakhi zofuzo ze-MLL, kanye nesikhashana, ukuguqulwa kwe-CEBPA noma i-NPM1.

Kodwa-ke, njengoba kuboniswe ekutadisheni kwe-NEJM yakamuva, izigaba ze-WHO ze-WHO azisebenzi kahle inani elikhulu lama-AML amacala. Esicwaningweni, iziguli ezingu-736 ezine-AML, noma amaphesenti angu-48 zazo, zazingeke zihlukaniswe ngokusekelwe emaqenjini e-WHO, nakuba amaphesenti angama-96 alawo mkhuba enza kanjalo, okuthiwa izinguquko zomshayeli-izinguquko zofuzo ukulimala.

Ukutholakala kwamagciwane amaningi omusha we-leukemia, ukuguquguquka okuningi komshayeli ngesiguli, kanye namathrafikhi aguquguqukayo awenza abaphenyi babuyekeze kabusha ukuhlukaniswa kwe-AML kusukela ekuqaleni.

Ukuhlaziywa kwe-AML nokuHlelwa, ngokusekelwe ku-Genetic Mutations

Ngakho-ke, abacwaningi babuyela ebhodini lokudweba ukuze bazame ukuthuthukisa uhlelo olusha lokuhlukanisa i-AML esebenzisa ulwazi olusakhulayo.

Isigaba esamukelekayo kakhulu kanye nezinhlelo zokubikezela i-AML zisebenzisa isigaba se-WHO - kuhlanganise nezinto okuthiwa i-cytogenetic lesions-isibonelo t (15; 17) -nonke ne-NPM1, FLT3ITD, ne-CEBP, njengoba kubhalwe ngenhla.

Ngenxa yocwaningo olusha, abalobi bancoma ukuthi, ngesikhathi esifushane, i-TP53, i-SRSF2, i-ASXL1, i-DNMT3A, ne-IDH2 kufanele icatshangelwe ukuthi ifakwe emibhalweni yokubikezela ngoba ijwayelekile futhi ithonya elinamandla emiphumeleni yomtholampilo.

Ngokwezigaba ze-AML, ukuhlolwa kwe-"splicing-factor genees" i-RUNX1, i-ASXL1, ne-MLLPTD ekuxilongweni kuyokwazi ukubona iziguli "eqenjini le-chromatin-spliceosome." Leli yiqembu lesibili elikhulu kunazo zonke iziguli ze-AML esifundweni, futhi ngokungafani Amakilasi we-AML, ayikho isifo esisodwa sezakhi zofuzo esichaza leli qembu.

Ukusebenzisa le nqubo ehlongozwayo, iziguli ezingu-1,236 ezinezinguquko ezingu-1,540 zingafakwa esigabeni esisodwa, kanti iziguli ezingu-56 zihlangene nezigaba ezimbili noma ngaphezulu. Isiguli seziguli ezingu-166 ezinezinguquko zomshayeli zahlala zingenakulinganiswa.

Ingemuva yezinhlelo zokuHlelwa ezikhona

I-AML ayifakiwe njengezinye eziningi kansela. Umbono womuntu onama-AML uncike kunolunye ulwazi, njenge-subtype njengoba kunqunywe ukuhlolwa kwelebhu, kanye neminyaka yesiguli, neminye imiphumela yokuhlolwa kwelebhu.

I-AML subtypes ingahlobana nesimo sengqondo somuntu ngamunye kanye nokwelashwa okungcono kakhulu. Isibonelo, i-acute promyelocytic leukemia (APL) i-subtype ivame ukuphathwa ngokusebenzisa izidakamizwa ezihlukile kulabo asetshenziselwa ezinye izansi ze-AML.

Izinhlelo ezimbili eziyinhloko ezisetshenziselwe ukuhlukanisa i-AML zibe yi-subtypes yizigaba zeFrench-American-British (FAB) kanye nesigaba esisha se-World Health Organization (WHO).

Isigaba samaFrench-American-British (FAB) se-AML

Ngawo-1970, iqembu lamaFrench, eMelika, naseBrithani ochwepheshe be-leukemia bahlukanisa i-AML yaba yi-subtypes, i-M0 kuya kwe-M7, ngokususelwa kuhlobo lwesitembu lapho i-leukemia iqala khona nokuthi amangqamuzana avuthiwe kangakanani. Lokhu kwakusekelwe ngokuyinhloko ngokuthi amangqamuzana e-leukemia ayebheke kanjani ngaphansi kwe-microscope ngemuva kokugqoka izinqubo.

Igama le-FAB subtype

M0 Undifferentiated acute leyemia ye-myeloblastic

M1 I-leukemia elula ye-myeloblastic ene-maturation encane

I-M2 i-leukemia e-myeloblastic enamandla ne-maturation

I-M3 Acute promyelocytic leukemia (APL)

I-M4 i-myelomonocytic i-leukemia

I-M4 eos I-myelomonocytic i-leukemia elula ne-eosinophilia

I-M5 i-leukemia ye-monocytic elula

I-M6 i-leyemia ye-erythroid elula

I-M7 I-leukemia ye-megakaryoblastic elula

I-Subtypes M0 ngokusebenzisa i-M5 yonke iqala ngamafomu amancane amangqamuzana egazi elimhlophe. I-M6 AML iqala ngamafomu alula kakhulu amangqamuzana egazi obomvu, kuyilapho i-M7 AML iqala emafomini amasha angamafomu enza amaplatelets.

I-World Health Organization (WHO) isigaba se-AML

Uhlelo lwesigaba se-FAB luwusizo kanti lusasetshenziselwa ukuqoqa i-AML ibe yi-subtypes, kodwa ulwazi oluhambelana nokubikezela kanye nokubuka izinhlobo ezahlukene ze-AML, kanti enye yalezi zintuthuko kuboniswe ohlelweni luka-2008 lwe-World Health Organization (WHO).

Uhlelo lwe-WHO luhlukanisa ama-AML ngamaqembu amaningana:

I-AML enezinhlobo ezithile ezingavamile

I-AML nezinguquko ezihlobene nemyelodysplasia

I-AML ihlobene ne-chemotherapy yangaphambilini noma imisebe

I-AML ayihlongozwanga ngenye indlela (i-AML engangeni kwelinye lamaqembu angenhla futhi ngenxa yalokho ihlukaniswe ngokufana nalokho okwenziwe ohlelweni lwe-FAB):

I-myeloid sarcoma (eyaziwa ngokuthi i-granulocytic sarcoma noma i-chloroma)

Ukwanda kweMyeloid okuhlobene ne-Down syndrome

I-leukemias e-undifferentiated ne-biphenotypic
Lezi yi-leukemias ezinezici ezimbili ze-lymphocytic kanye nemyeloyelo. Ngezinye izikhathi kuthiwa yi-ALL ngezimpawu ze-myeloid, i-AML enezimpawu ze-lymphoid, noma ama-leukemi ase-acute.

Ngaphezulu kwalezi zigaba ze-WHO zashintshwa kusukela ku-American Cancer Society.

Imithombo:

Papaemmanuil E, Gerstung M, et al. Ukuhlukaniswa kwe-genomic nokubikezela ku-leukemia ephawulekayo ye-myeloid. N Engl J Med . 2016; 374 (23): 2209-21.

I-Wellcome Trust Sanger Institute. I-myeloid leukemia enamandla kakhulu okungenani izifo ezingu-11 ezahlukeneyo. Kufinyelelwe ngo-June 2016.

I-American Cancer Society. Kanjani i-leukemia ephawulekayo ye-myeloid? Kufinyelelwe ngo-June 2016.