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Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy

We evaluate clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)-directed therapy. Among the 16 B-ALL and 8 T-ALL subtypes identified by next generation sequencing, ETV6-RUNX1, high-hyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates (95% to 98.4%); TCF3-PBX1, PAX5alt, T-cell, ETP, iAMP21, and hypodiploid ALL intermediate rates (80.0% to 88.2%); and BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like and KMT2A-rearranged ALL the worst rates (64.1% to 76.2%). All but three of the 142 patients with day-8 blood MRD <0.01% remained in remission. Among new subtypes, intensified therapy based on day-15 MRD≥1% improved outcome of DUX4-rearranged, BCR-ABL1-like, and ZNF384-rearranged ALL, and achievement of day-42 MRD<0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged and ETV6-RUNX1-like ALL. Thus, new subtypes including DUX4-rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2D-rearranged and ZNF384-rearranged ALL have important prognostic and therapeutic implications.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006609 Illumina HiSeq 2000 Illumina NovaSeq 6000 122
EGAD00001007530 Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina HiSeq 4000 Illumina NovaSeq 6000 NextSeq 550 227
Publications Citations
Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy.
Blood Cancer Discov 2: 2021 326-337
43
Acute lymphoblastic leukemia displays a distinct highly methylated genome.
Nat Cancer 3: 2022 768-782
8
The genomic landscape of pediatric acute lymphoblastic leukemia.
Nat Genet 54: 2022 1376-1389
65
A convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1.
NAR Cancer 4: 2022 zcac041
0
Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response.
Nat Med 29: 2023 170-179
13