Ukuthuthuka Ekuhlukanisweni Kwezingozi ze-T-ALL: Ukuhlukaniswa Okusekelwe ku-NGS Kukhomba Amaqembu Angaphansi Anengozi Ephakeme
Ocwaningweni oluyimpumelelo olushicilelwe ku- Igazi, abacwaningi basebenzise ukulandelana kwesizukulwane esilandelayo (NGS) ukuthuthukisa ukuhlukaniswa kwengozi ye-T-cell acute lymphoblastic leukemia (T-ALL). Lolu hlelo lokuhlela oluthuthukisiwe lunikeza indlela enembile yokubikezela imiphumela yesiguli nokuhlonza amaqembu amancane asengozini enkulu, okungenzeka ukuthi kuvulwe umnyango wamasu okwelapha enziwe ngokwezifiso.
Lolu cwaningo, olwaluhlanganisa iziguli ezingu-198 zabantu abadala ze-T-ALL ezivela esivivinyweni se-GRAALL-2003/2005 kanye neziguli ezingu-242 zezingane ze-T-ALL ezivela esivivinyweni se-FRALLE2000T, lusebenzise ukulandelana kwe-whole-exome okuqondisiwe ukuhlola izakhi zofuzo ezingu-72 ezihlobene nomdlavuza. Phakathi kokutholakele, izakhi zofuzo ze-NOTCH1 zazivame kakhulu kubantu abadala, ezikhona ku-77% wamacala, kulandelwa izakhi zofuzo ze-CDKN2A (66%) kanye ne-PHF6 (50%). Lokhu kuphrofayili yezakhi zofuzo okuningiliziwe kwenza abacwaningi bakwazi ukuhlukanisa iziguli ngezigaba ezinobungozi obukhulu kanye nezinobungozi obuphansi, okunomthelela omkhulu ekubikezelweni kwazo.
Kwasungulwa uhlelo olusha lokuhlukanisa olusekelwe ku-NGS, olubonise amakhono aphezulu okubikezela amazinga okubuyela emuva aqongelelekayo, ukusinda okuphelele, kanye nokusinda okungenazifo uma kuqhathaniswa nezindlela zangaphambilini. Ucwaningo luthole iziguli ezisengozini encane njengalezo ezithwala izinguquko ezithile (isb., NOTCH1/FBXW7, PHF6, EP300) ngaphandle kokushintsha okwengeziwe okuyingozi kakhulu (isb., izinguquko endleleni ye-PI3K, TP53, kanye ne-IDH1/2). Lezi ziguli zazinezinga lokubuyela emuva eliqongelelekayo leminyaka emi-5 (CIR) elingama-21%, kanti lezo ezisesigabeni esinobungozi obukhulu zibhekene ne-CIR ephezulu kakhulu engama-47%.
Ngaphezu kwalokho, ukuhlanganisa okutholakele kwe-NGS nezici zezokwelapha ezifana nenani lamaseli amhlophe egazi (i-WBC) kanye namazinga amancane esifo esisele (i-MRD) kwaholela emodelini yobungozi ehlanjululwe kahle eyahlukanisa iziguli ngamaqembu amathathu: ezisengozini enkulu, ezisengozini ephakathi nendawo, kanye nezisengozini encane. Le modeli yabonakala isebenza kahle kakhulu ekuhlukaniseni iziguli ezingazuza ekwelashweni okunamandla kakhulu, ikakhulukazi lezo ezinephrofayili yofuzo enobungozi obukhulu.
Okutholakele kocwaningo kugcizelela amandla e-NGS okuthuthukisa izibikezelo zokubikezela isifo nokuthuthukisa ukuhlela ukwelashwa kweziguli ze-T-ALL zabantu abadala kanye nezingane. Ngokuhlanganisa ukuqonda kwezakhi zofuzo nedatha yezokwelapha, odokotela bangakwazi ukubona kangcono iziguli ezingase zizuze ekwelashweni okuqondiwe okuvelayo, njenge-PI3K inhibitors kanye ne-IDH1/IDH2 inhibitors ekhethiwe.
Njengoba ucwaningo luvula indlela yamasu okwelapha aqondene nawe, luphindeo iphakamisa imibuzo ebalulekile mayelana nokusebenza kwalolu hlobo lwesifo ezinhlotsheni ezahlukene kanye nezindlela zokwelapha zesimanje. Nakuba ukuhlukaniswa kwezifo okusekelwe ku-NGS kunesithembiso, kudingeka ucwaningo olwengeziwe ukuqinisekisa ukusebenza kwayo kubantu abahlukahlukene kanye nokuthuthukisa indlela yamacala ayinselele, njengalawo ane-T-ALL engaphikisi.