Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

• DOI: 10.1182/bloodadvances.2021005634
• Publication Date: 2021-12-21T22:01:19Z
• Authors: Thai Hoa Tran; Sylvie Langlois; Caroline Meloche; Maxime Caron; Pascal Saint-Onge; Alexandre Rouette; Alain R. Bataille; Camille Jimenez-C...; Thomas Sontag; Henrique Bittencourt; Caroline Laverdière; Vincent-Philippe ...; Jean-Marie Leclerc; Peter D. Cole; Lisa M. Gennarini; Justine M. Kahn; Kara M. Kelly; Bruno Michon; Raoul Santiago; Kristen E. Stevenson; Jennifer J. G. Welch; Kaitlin M. Schroeder; Victoria Koch; Sonia Cellot; Lewis B. Silverman; Daniel Sinnett
• Keywords: ETV6

Abstract The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many which are cryptic conventional cytogenetics. RNA sequencing (RNA-seq) a powerful next-generation technology that can simultaneously identify gene rearrangements, sequence mutations and expression profiles in single assay. We examined the feasibility utility incorporating RNA-seq into prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients who consented to optional studies had samples available RNA-seq. identified at least 1 alteration 157 (91%). Fusion detection was 100% concordant results obtained from cytogenetic analyses. An additional 56 fusions were RNA-seq, confer or therapeutic significance. Gene profiling enabled further classification following B-cell (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like 31), TCF3-PBX1 7), KMT2A-rearranged (KMT2A-R; n 5), intrachromosomal amplification chromosome 21 (iAMP21) 1), hypodiploid Philadelphia (Ph)-positive/Ph-like 16), DUX4-R 11), PAX5 alterations (PAX5 alt; P80R ZNF384-R 4), NUTM1-R MEF2D-R others 10). 141 nonsynonymous 93 (54%); most frequent RAS-MAPK pathway mutations. Among 79 both low-density array data chromosome-like signature prediction, 74 (94%). In conclusion, several clinically relevant not detected methods, supports integration this front-line pediatric trials. This registered www.clinicaltrials.gov as #NCT03020030.