Ukuqhubela phambili kwi-T-ALL Risk Stratification: Udidi oluSekelwe kwi-NGS luchonga amaqela amancinci anomngcipheko ophezulu

Kwisifundo esiphumeleleyo esapapashwa kwi Igazi, abaphandi basebenzise i-next-generation sequencing (NGS) ukuphucula ulwahlulo lomngcipheko we-T-cell acute lymphoblastic leukemia (T-ALL). Le nkqubo yokwahlulahlula ephuculweyo inika indlela echanekileyo yokuqikelela iziphumo zesigulana kunye nokuchonga amaqela amancinci anomngcipheko ophezulu, okunokuvula ucango lwezicwangciso zonyango ezenzelwe wena.

Olu phononongo, olwaluquka izigulane ezili-198 zabantu abadala ze-T-ALL ezivela kuvavanyo lwe-GRAALL-2003/2005 kunye nezigulane ezingama-242 ze-T-ALL zabantwana ezivela kuvavanyo lwe-FRALLE2000T, lusebenzise ulandelelwano olujoliswe kwi-whole-exome ukuhlola ii-genes ezingama-72 ezinxulumene nomhlaza. Phakathi kwezinto ezifunyenweyo, ii-mutations ze-NOTCH1 zezona zixhaphakileyo kubantu abadala, ezikhoyo kwi-77% yamatyala, zilandelwa zii-mutations ze-CDKN2A (66%) kunye nee-mutations ze-PHF6 (50%). Olu hlalutyo oluneenkcukacha lwe-genetic lwenze abaphandi bakwazi ukwahlula izigulane kwiindidi ezinobungozi obuphezulu kunye nezinobungozi obuphantsi, nto leyo enefuthe elibalulekileyo kwi-prognosis yazo.

Inkqubo entsha yokwahlulahlula esekwe kwi-NGS yaphuhliswa, eyabonisa amandla aphezulu okuqikelela amazinga okubuyela umva kwakhona, ukusinda ngokubanzi, kunye nokusinda okungenazifo xa kuthelekiswa neendlela zangaphambili. Olu phononongo luchonge izigulane ezisengozini ephantsi njengezo zithwala utshintsho oluthile (umz., i-NOTCH1/FBXW7, i-PHF6, i-EP300) ngaphandle kotshintsho olongezelelweyo olunomngcipheko ophezulu (umz., utshintsho kwindlela ye-PI3K, i-TP53, kunye ne-IDH1/2). Ezi zigulane zazinezinga lokubuyela umva eliqokelelweyo leminyaka emi-5 (i-CIR) engama-21%, ngelixa ezo zikwicandelo elinomngcipheko ophezulu zijongene ne-CIR ephezulu kakhulu engama-47%.

Ngaphezu koko, ukudibanisa iziphumo ze-NGS kunye nezinto zonyango ezifana nenani leeseli zegazi ezimhlophe (i-WBC) kunye namanqanaba amancinci esifo esisele (i-MRD) kukhokelele kwimodeli yomngcipheko ocociweyo owahlula izigulane zibe ngamaqela amathathu: ezinobungozi obuphezulu, ezinobungozi obuphakathi, kunye nezinobungozi obuphantsi. Le modeli ibonakalise ukusebenza kakuhle ekuhlukaniseni izigulane ezinokuxhamla kunyango olunamandla ngakumbi, ngakumbi ezo zineprofayili yemfuza enobungozi obuphezulu.

Iziphumo zophando zigxininisa amandla e-NGS okuphucula uqikelelo lokubikezela isifo kunye nokuphucula ucwangciso lonyango kubantu abadala kunye nabantwana abane-T-ALL. Ngokudibanisa ulwazi lwezakhi zofuzo kunye nedatha yeklinikhi, oogqirha banokuchonga ngcono izigulana ezinokungenelwa kunyango oluvelayo olujoliswe kulo, olufana ne-PI3K inhibitors kunye ne-selective IDH1/IDH2 inhibitors.

Njengoko olu phononongo luvula indlela yezicwangciso zonyango ezenzelwe wena, lukwavulao iphakamisa imibuzo ebalulekileyo malunga nokusebenza kolu hlobo kwiintlanga ezahlukeneyo kunye neendlela zonyango zanamhlanje. Nangona ukwahlulwahlulwa okusekwe kwi-NGS kuthembisa, uphando olongezelelekileyo luyafuneka ukuqinisekisa ukusebenza kwayo kumaqela ahlukeneyo kunye nokuphucula indlela yamatyala anzima, njengalawo ane-T-ALL enganyangekiyo.