Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young

Kimura S, Polonen P, Montefiori L, Park CS, Iacobucci I, Yeoh AE, Attarbaschi A, Moore AS, Brown A, Manabe A, Buldini B, Freeman BB, Chen C, Cheng C, Kean Hui C, Li CK, Pui CH, Qu C, Tomizawa D, Teachey DT, Varotto E, Paietta EM, Arnold ED, Locatelli F, Escherich G, Elisa Muhle H, Marquart HV, de Groot-Kruseman HA, Rowe JM, Stary J, Trka J, Choi JK, Meijerink JPP, Yang JJ, Takita J, Pawinska-Wasikowska K, Roberts KG, Han K, Caldwell KJ, Schmiegelow K, Crews KR, Eguchi M, Schrappe M, Zimmerman M, Takagi M, Maybury M, Svaton M, Reiterova M, Kicinski M, Prater MS, Kato M, Reyes N, Spinelli O, Thomas P, Mazilier P, Gao Q, Masetti R, Kotecha RS, Pieters R, Elitzur S, Luger SM, Mitchell S, Pruett-Miller SM, Shen S, Jeha S, Köhrer S, Kornblau SM, Skoczeń S, Miyamura T, Vincent TL, Imamura T, Conter V, Tang Y, Liu YC, Chang Y, Gu Z, Cheng Z, Yinmei Z, Inaba H, Mullighan CG. Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young. medRxiv. 2023 Nov 8;. doi: 10.1101/2023.11.06.23298028. PubMed PMID: 37986997; PubMed Central PMCID: PMC10659466.

Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease. We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing. Experimental modeling was used to examine the mechanistic impacts of genomic alterations. Therapeutic vulnerabilities were identified by high throughput drug screening of cell lines and xenografts.