Kubva pane Gene Study, AML Leukemia ine 11 Subtypes

by Tom Iarocci, MD

Leukemia haisi chirwere chimwe, asi vazhinji. Masayendisiti ari kutanga kunzwisisa kuti kunyange imwe chete, yakasiyana-siyana yeukemukemia ine maitiro akasiyana nenzira dzakakosha.

Zvine maitiro makuru eukemia anobva pane kuti angave akaoma here kana asingagumi, uye myeloid kana lymphocytic leukemias, uye izvi zvikamu zvikuru zvinotevera:

Muteyi mutsva (kana myelogenous) leukemia (AML)

Myeloid isingaperi (kana myelogenous) leukemia (CML)
Acute lymphocytic (kana kuti lymphoblastic) leukemia (ALL)
Chronic lymphocytic leukemia (CLL)

Pamusoro pe AML

Chirwere chinokonzerwa neukemia chinonzi kenza yemapfupa -mapapiro emapfupa, apo masero eropa anoitwa-uyewo chirwere cheropa.

AML inoonekwa se "acute" leukemia nekuti inokura nokukurumidza. Chikamu chechirevo chemashoko chinobva mumasero e-myeloid-boka remasero anowanzobudirira kuva marudzi akasiyana-siyana emasero eropa akakura, akadai semasero matsvuku eropa, masero masero eropa uye maplatelet.

AML ine zvipembenene zvakawanda: Zvakanaka myelogenous leukemia inozivikanwawo seyakakura myeloid leukemia, yakaoma myeloblastic leukemia, yakaoma granulocytic leukemia uye yakaoma nonlymphocytic leukemia.

AML inogona kukanganisa vanhu vezera rose. Sangano re World Health Organization ra2011 GLOBOCAN rakaratidza kuti vanhu 352 000 munyika yose vaiva AML, uye chirwere ichi chave chichiwedzera pakuwanda kwevanhu.

Zviratidzo nezviratidzo zve AML zvinosanganisira:

Fever
Uturu hunorwadza
Lethargy uye kuneta
Kupfupika kwemhepo
Pale pepa
Vanowanzorwara zvirwere
Zviri nyore kupwanya
Kubuda ropa kusinganzwisisiki, kwakadai sekuwanzova nosebleeds uye kubuda kubva mumasamu

Subtypes

Kurongeka kwe AML inotaridzika kuoneka kwemasero emukenza, kana kuti morphology, kuri kuwedzerwa nekuwanikwa kutsva pamusoro pemararamiro ekuchinja kana kushanduka kunoitwa nenzira dzakasiyana-siyana dzechirwere ichi.

Vatsvakurudzi veWorcomecome Trust Sanger Institute nevashandi munguva pfupi yapfuura vakawedzera kune zvidzidzo, ruzivo pamusoro pemararamiro ekuchinja kwemashoko anobatsira kuumba kunzwisisa kwe AML-kuwedzera kushandura pfungwa ye AML kubva kune imwe chirwere chimwe kune imwe inenge 11 dzakasiyana siyana dzemarudzi kuora mwoyo , nekusiyana-siyana kunogona kubatsira kutsanangura nguva dzakasiyana-siyana dzokurarama pakati pevaduku vaduku vane AML.

Vatsvakurudzi vakabudisa ruzivo rwavo pamusoro peiyo genetic ya AML mumagazini yaJune 2016 ye "New England Journal of Medicine," uye nyanzvi dzinofunga kuti zvitsva izvi zvinogona kuvandudza kuongororwa kwechirwere uye kuchinja nzira iyo varwere vane AML vanoongororwa uye vanobatwa mune remangwana.

NeJM Chidzidzo

Vatsvakurudzi vakaongorora varwere vane 1 540 vane AML avo vakanyoreswa mumakiriniki. Vakatsvaga mazana emagetsi zana anozivikanwa kuti anokonzera kubatwa neukemia nechinangwa chekuziva "mazita ekuberekwa" shure kwekuvandudzwa kwechirwere.

Vakaona kuti varwere vane AML vanogona kugoverwa kuva mazana mapoka makuru mazana mana, rimwe nerimwe rine magirasi akasiyana-siyana ekuchinja kwechimiro uye maitiro akasiyana uye zvinhu. Maererano nekudzidza, varwere vazhinji vaiva nehumwe humwe humwe hutano hwekuchinja hunoita kuti vawane houkemia, iyo inogona kubatsira kutsanangura kuti sei AML ichiratidza kuchinja kwakadaro mukupona kwemazinga.

Zvinetso

Kuziva ruzivo rwekugadzirwa kwehutachiona rwehutachiona kunogona kuvandudza kukwanisa kufanotaura kana zvirwere zvino zvingashanda. Ruzivo rworudzi urwu runogona kushandiswa kugadzira mishonga yekliniki matsva kuti iwedzere kurapa kwakanakisisa kune rimwe nerimwe AML subtype; uye pakupedzisira, huwandu hwakawanda hwekuongorora mazita eAML pahutano hunova hunova hunoitika.

Muna 2008 World Health Organization (WHO) inorongwa, masayendisiti atotanga kurongedza munhu mukuru AML mu "ma molecular" maitiro akasiyana-siyana, kusanganisira kuchinja mazita emagetsi kana kuti kukuvadzwa kwekromosomes inoratidzirwa seizvi: t (15; 17), t (8; 21) ), inv (16) -t (16; 16), t (6; 9), inv (3) -t (3; 3), MLL fusion genes, uye nguva, CEBPA kana NPM1 kuchinja.

Zvisinei, sezvakaratidzwa munyaya yezvino ye NEJM yekudzidza, WHO iyo molecular classifications haishande zvakanaka nokuda kwemahombe akawanda ema AML. Muchidzidzo chacho, 736 varwere vane AML, kana 48 muzana yavo, vangadai vasina kuiswa mumapoka e WHO, kunyange zvazvo 96 muzana yevarwere vakaita, zvechokwadi, vane zvinonzi mutori-mutengesi-genetic kuchinja kuipa.

Kuwanikwa kwemajini mazhinji matsva eukemia, kutengesa kwakawanda kwevatengesi nemurwere, uye kushanduka kwemaitiro kwakakonzera kuti vaongorori vaongororezve maitiro eAAML kubvira pakutanga.

Zvakarongwa AML Kuongorora uye Kurongeka, Kubva kuGenetic Mutations

Nokudaro, vatsvakurudzi vakadzokera kumabhodhi kuti vaedze kuvaka shanduro itsva yekuisa mukana AML iyo inoshandisa shanduko yakabuda.

Chirongwa chinonyanyobvumirwa zvikuru uye zvirongwa zvekufananidzira kweAAM zvinoshandisa sangano re WHO-kusanganisira iyo inonzi cytogenetic-lesions-somuenzaniso (15; 17) -kuzara neNPM1, FLT3ITD, uye CEBP, sezvakanyorwa pamusoro apa.

Mukuona kwechidzidzo chitsva, vanyori vakurudzira kuti, munguva pfupi, TP53, SRSF2, ASXL1, DNMT3A, uye IDH2 inofanira kufungidzirwa nokuda kwekubatanidzwa mumitemo yekufananidzira nekuti inowanzoita simba guru pamigumisiro yezvipatara.

Pamusangano we AML, kuongororwa kwe "splicing-factor genes" RUNX1, ASXL1, uye MLLPTD pakuongororwa kunogona kuziva varwere vari mu "boka re chromatin-spliceosome." Uyu waiva wechipiri mukuru wevarwere ve AML mukudzidza, uye kusiyana Masangano eWMS ye AML, hapana rimwe ruzivo rwegeneti rinotsanangura boka iri.

Achishandisa chirongwa ichi chinorongedzwa, 1 236 vevarwere 1,540 vane kuchinja kwekutyaira kunogona kuiswa muboka rimwe chete, uye varwere 56 vakawana nzira dzezvikamu zviviri kana kupfuura. Chimwe chevanhu 166 vane zvirwere zvekufambisa mutambi vakaramba vasina chimiro.

Mheyo yeChirangaridzo yeChirongwa

AML haisati yakarongedzwa sevamwe vakawanda kanzira. Maonero omunhu ane AML anongotarisa pane mamwe mashoko, akadai sekaypeti inotsanangurwa neongororo yebazi, pamwe nezera remurwere, uye mamwe emigumisiro yemuedzo.

AML subtypes inogona kurondedzera maonero omurwere mumwe nomumwe uye kurapa kwakanakisisa. Semuenzaniso, iyo acute promyelocytic leukemia (APL) subtype inowanzobatwa nekushandisa zvinodhaka zvakasiyana kune izvo zvinoshandiswa kune dzimwe subtypes dze AML.

Zvitatu zvehurongwa hukuru hwakashandiswa kuisa AML ku subtypes ndeyekuFrance-American-British (FAB) nekugadzirisa uye nhengo itsva yeWorld Health Organization (WHO).

Chikamu cheFrench-American-British (FAB) che AML

Muma1970, boka reFrench, America, neBrithani leukemia nyanzvi rakaparadzanisa AML mu subtypes, M0 kusvika M7, zvichienderana nerudzi rwechiremera iro rinokonzerwa neukemia uye kuti yakakura sei masero. Izvi zvaive zvakanyanya kunyanya kuti masero eukemia anotarisa sei pasi pe microscope mushure mekunyadzisa nguva dzose.

FAB subtype Zita

M0 Undifferentiated acute myeloblastic leukemia

M1 Acute myeloblastic leukemia nekunyorera kusakwana

M2 Acute myeloblastic leukemia nekukura

M3 Acute promyelocytic leukemia (APL)

M4 Yakanyanya myelomonocytic leukemia

M4 eos Inoshandisa myelomonocytic leukemia ine eosinophilia

M5 Acute monocytic leukemia

M6 Yakanyanya erythroid leukemia

M7 Acute megakaryoblastic leukemia

Zvikamu zveM0 kuburikidza neM5 zvose zvinotanga mumasero asina kuchena emasero machena eropa. M6 AML inotanga mumasero mashoma emasero matsvuku eropa, apo M7 AML inotanga mumhando dzisina kufanana dzemasero anoita maplatelet.

World Health Organization (WHO) yakarongeka ye AML

IFAB classification system inobatsira uye inowanzoshandiswa kushanyira AML ku subtypes, zvisinei, ruzivo rwakafambira mberi maererano nehuwandu hwekufananidzira uye maonero emhando dzakasiyana dzeAAM, uye zvimwe zvekufambira mberi uku zvakaratidzwa muHurumende yeWorld Health Organization (WHO) ye2008.

Nzira ye WHO inoparadzanisa AML mumapoka akawanda:

AML mune mamwe maitiro ekusaremara

AML ine translocation pakati pemakromosomes 8 ne21
AML ine translocation kana inversion mu chromosome 16
AML ine translocation pakati pemakromosomes 9 ne11
APL (M3) ine translocation pakati pemakromosomes 15 ne17
AML ine translocation pakati pemakromosomes 6 ne9
AML ine translocation kana inversion mu chromosome 3
AML (megakaryoblastic) ine translocation pakati pemakromosomu 1 ne22

AML ne myelodysplasia-related changes

AML yakabatana nechemotherapy yapfuura kana kuti rayation

AML kwete zvakataurirwa (AML iyo haina kuwira mune rimwe remapoka ari pamusoro apa saka rinorondedzerwa zvakafanana nezvakaitwa muFAB system):

AML ine minimal differentiation (M0)
AML pasina kusimwa (M1)
AML nekunakisa (M2)
Acute myelomonocytic leukemia (M4)
Acute monocytic leukemia (M5)
Acute erythroid leukemia (M6)
Acute megakaryoblastic leukemia (M7)
Zvakanaka zvinoshandiswa neukemia
Acute panmyelosis ne fibrosis

Myeloid sarcoma (inozivikanwawo se granulocytic sarcoma kana chloroma)

Kuwedzerwa kweMyeloid kwakabatana neA Down syndrome

Undifferentiated uye biphenotypic acute leukemias :
Idzi ndiyeukemias dzine zvose zvinokonzera lymphocytic uye myeloid. Dzimwe nguva inonzi ALL ne myeloid markers, AML nevatambi ve lymphoid, kana kuti vakavhenganiswa nemakucu eukisi.

Pamusoro-soro WHO maitiro akashandurwa kubva kuAmerican Cancer Society.

_Sources:

_{Papaemmanuil E, Gerstung M, et al.} _{Genomic classification uye kufungidzira mune zvakanyanya myeloid leukemia.} _{N Engl J Med .} _{2016; 374 (23): 2209-21.}

_{Wellcome Trust Sanger Institute.} _{Chirwere chemyeloid chinokonzerwa nehutachiona chinokwana 11 zvirwere zvakasiyana.} _{Yakasvika muna June 2016.}

_{American Cancer Society.} _{Ndeipi inonzi acute myeloid leukemia yakarongwa?} _{Yakasvika muna June 2016.}