Guhinduka kwa gene imwe byerekana ingaruka mbi muri leukemia ikuze
Guhinduka kwa gene imwe byerekana ingaruka mbi muri leukemia ikuze
Anonim

Kurandura ADN y'umugore wapfuye azize indwara ya myeloid leukemia (AML) yatumye abashakashatsi bo mu Ishuri Rikuru ry’Ubuvuzi rya kaminuza ya Washington i St.

Ibyavuye mu bushakashatsi, niba byemejwe mu bushakashatsi bunini, byerekana ko ikizamini cyo gusuzuma ihinduka ry’imiterere ya gene gishobora kumenya abarwayi ba AML bakeneye ubuvuzi bukabije kuva bagitangira. Ubuvumbuzi bushya butanga kandi intego ifatika yo guteza imbere imiti irwanya AML, kanseri y'amaraso yihuta yica Abanyamerika 9 000 000 buri mwaka.

Abashakashatsi bakoze ubushakashatsi ku barwayi bagera kuri 300 AML, abashakashatsi basanze abafite ihinduka ry’imiterere ya ADN methyltransferase 3A, cyangwa DNMT3A, barokotse hagati y’umwaka urenga nyuma yo kwisuzumisha, ugereranije n’imyaka igera kuri 3.5 kubadafite ihinduka. Ubushakashatsi bwatangajwe kumurongo wa 10 Ugushyingo mu kinyamakuru cyitwa New England Journal of Medicine.

Ikigaragara ni uko abashakashatsi basanze ihinduka ry’imihindagurikire ya kimwe cya gatatu cy’abarwayi bafite ibimenyetso bitazwi neza, hashingiwe ku bizamini byo gusuzuma. Aba barwayi mubisanzwe bahabwa imiti ya chimiotherapie nkumuti wambere.

Umwanditsi mukuru Richard K. agira ati: "Ukurikije ibyo twasanze, niba umurwayi afite ihinduka rya DNMT3A, bisa nkaho ushaka kuvura bikabije, wenda ugahita uhindurwamo amagufwa cyangwa uburyo bwa chimiotherapie bukomeye". Wilson, PhD, umuyobozi w'ikigo cya Genome cya kaminuza ya Washington akaba n'umwarimu wa genetika na mikorobe ya molekile.

Ubushakashatsi bwakozwe nitsinda rinini ryabahanga mu kigo cya Genome hamwe n’ikigo cya kanseri cya Siteman ku bitaro bya Barnes-Abayahudi ndetse n’ishuri ry’ubuvuzi rya kaminuza ya Washington. Ni abambere mugukoresha uburyo bwuzuye, bugizwe na genome muguhishura ishingiro rya kanseri. Mugukoresha genome - ADN zose - z'abarwayi ba kanseri hamwe na selile zabo, barashobora kubona ihinduka rikomeye kumuzi yindwara. Noneho, abashakashatsi barashobora gushakisha ayo makosa kubandi barwayi.

Ubushakashatsi bushya bujyanye n’akazi abahanga mu bumenyi bwa genoside bo muri kaminuza ya Washington bakora mu rwego rwa Kanseri Genome Atlas, umushinga uhuriweho n’ikigo cy’igihugu gishinzwe kanseri n’ikigo cy’igihugu gishinzwe ubushakashatsi ku bantu kugira ngo ugaragaze ishingiro ry’imiterere y’ubwoko burenga 20 bwa kanseri..

Umuyobozi w'ikigo cy'igihugu gishinzwe ubuzima, Francis Collins, MD, PhD, agira ati: "Ubu buvumbuzi ni urugero rugaragara rw'imbaraga zo gusesengura byimazeyo genoside ya kanseri." "Mu gukoresha ADN ikurikirana cyane, abashakashatsi bazashobora kuvumbura impinduka zose zisanzwe zigira uruhare muri kanseri. Hamwe n'ubumenyi, hazashyirwaho urutonde rw’imiti igamije kurwanya indwara, hashingiwe ku myumvire ihamye y’ibinyabuzima ku ndwara."

Abashakashatsi bashize amanga kuri mutation ya DNMT3A bakoresheje genome yumugore wapfuye azize AML afite imyaka 50 bakayigereranya na genome ya selile. Hanyuma bareba niba gene DNMT3A yahinduwe muri selile ya leukemia kuva kubandi barwayi 281 bafite AML. Basanze ihinduka rya 62 muri bo, cyangwa 21 ku ijana.

Ikigaragara cyane ariko, basanze ihinduka rya DNMT3A kuri 34 ku ijana (56 kuri 166) by’abarwayi bari barashyizwe mu kaga nk’impanuka zo hagati, bashingiye ku isesengura rya chromosomes mu ngirabuzimafatizo zabo. Abaganga bakunze kureba kuri chromosomes kugirango bamenye aho batandukaniye kandi bongeye kwisubiraho, bikaba byerekana uburemere bwindwara.

Kurenga kimwe cya kabiri cyabarwayi ba AML bafite iyi profile-rishobora kubaho. Chromosomes zabo zisa nkibisanzwe cyangwa bifite impinduka nto cyane. Mugihe bamwe bakora neza kuri chimiotherapie isanzwe, abandi benshi bakora nabi. Kandi muriyo harimo ikibazo.

Umwanditsi mukuru akaba n'umuhanga mu kuvura indwara z'amaraso witwa Timothy Ley, MD, Lewis T. na Rosalind B. Umwarimu w’ubuvuzi wa Apple akaba n'umwarimu w’irondakoko, agira ati: "Ntabwo twagize uburyo bwizewe bwo kumenya umwe muri aba barwayi bazitabira ubuvuzi busanzwe." "Mu manza twize, ihinduka ry’imiterere ya gene DNMT3A rivuga ibindi byose twabonye kugeza ubu kugira ngo tumenye ingaruka mbi muri AML ishobora guhura n'ingaruka."

Mu rwego rw’ubushakashatsi bushya, abashakashatsi barebye kureba imiti abarwayi bahawe n’uburyo bamerewe. Abafite ihindagurika rya DNMT3A bavuwe no guterwa amagufwa baramba kurusha abahawe imiti ya chimiotherapie gusa, ariko abashinzwe iperereza baributsa ko urugero rw’icyitegererezo ari ruto. Bavuga ko hakenewe ubushakashatsi kugira ngo hemezwe inyungu zo guterwa amagufwa muri aba barwayi.

Abarwayi barengeje imyaka 60 bitwaye nabi cyane niba bafite mutation ya DNMT3A. Muri 17 bari mu bushakashatsi, nta numwe wabayeho igihe kirenze amezi 18.

Abashakashatsi ntibasanze ihinduka rya DNMT3A ku barwayi 79 bafite chromosomes bagaragaje ko bafite "ingaruka nziza." Abo barwayi bategerejweho kwitabira neza imiti isanzwe.

AML ni kanseri ikaze ya selile ikora amaraso mumitsi. Kimwe na kanseri nyinshi, bituruka ku ihindagurika ryirundanya muri ADN y'abantu mu myaka myinshi kandi ntabwo bituruka ku makosa yarazwe akivuka.

Biteganijwe ko muri Amerika hasuzumwa indwara zigera ku 13 000 000. Indwara iboneka cyane mubantu bakuru kandi bigoye kuyivura uko abarwayi basaza. Ikigereranyo cyimyaka 5 yo kubaho kubantu bakuru bafite AML ni 20%.

Gene ya DNMT3A ni ingenzi mugihe cyo gukura kwayo kandi ikora mumasemburo akora amaraso mubuzima bwumuntu. Abashakashatsi bo muri kaminuza ya Washington ntibaramenya uko ihinduka ry’imiterere ya gene rigira uruhare mu iterambere rya AML, ariko iki ni ikibazo cy’ibanze bagerageza gusubiza.

Ley abisobanura agira ati: "Guhindura DNMT3A bigaragara ko ari ingirakamaro ku buryo indwara ikura cyangwa igenda itera imbere kuko ihinduka ry’imihindagurikire rifite ingaruka zikomeye ku musaruro."

Mu barwayi bize, abashakashatsi basanze ihinduka 34 ritandukanye muri DNMT3A, ryanyanyagiye muri gene, rihindura imikorere ya gene muburyo butandukanye. Hatitawe ku bwoko bwihariye bwa mutation cyangwa aho buherereye muri gene, byose byari bifitanye isano no kubaho nabi.

Abashakashatsi bagaragaje ihinduka rya mbere rya DNMT3A igihe bakurikiranaga genome ya selile ya leukemia yakuwe ku mugore uri mu kigero cy'imyaka 50 nyuma yuko AML yongeye kugaruka nyuma yo kuvurwa bisanzwe. Mu mwaka wa 2008, iryo tsinda ryatangaje muri Kamere ko bakurikiranye ADN y’umurwayi ndetse na ADN bivuye ku ngirabuzimafatizo ya leukemia yafashwe igihe yamusuzumaga. Ntabwo bari babonye ihinduka rya DNMT3A icyo gihe kubera ko tekinoroji ya ADN ikurikirana itari yoroheje kandi yoroheje nkuko bimeze muri iki gihe.

Mu mezi menshi ari imbere, abashakashatsi bateganya ko amatsinda menshi yubushakashatsi azagenzura amabanki yabo ya selile y’abarwayi ba AML kugirango DNMT3A ihindurwe. Niba amakuru yabo yemeza ubushakashatsi bwa kaminuza ya Washington, hashobora gukorwa ikizamini cyo gusuzuma kugirango hamenyekane abarwayi bafite ihinduka ryimiterere.

Umwanditsi umwe witwa John DiPersio, MD, PhD, Virginia E. na Sam J. Goldman, umwarimu w’ubuvuzi, umuyobozi wa: Igice cya Oncology n'umuyobozi wungirije w'ikigo cya kanseri ya Siteman. "Ubu bushakashatsi butanga inzira n'ifatizo byo gukora nk'ibyo mu zindi ndwara mbi zose, zishobora gutuma habaho ibizamini bisuzumwa neza ndetse no kuvura neza."

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