Measurable residual disease monitoring of SPAG6, ST18, PRAME, and XAGE1A expression in peripheral blood may detect imminent relapse in childhood acute myeloid leukemia.

Overexpressed genes may be applicable for monitoring of measurable residual disease (MRD) in childhood acute myeloid leukemia (AML) patients without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n=53) and children with suspected infection (n=90). Gene expression at AML diagnosis (n=50) and during follow-up (n=21) was compared with child-specific reference values. At AML diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median five samples/patient, range 1-10) during follow-up in 21 patients with high expression at diagnosis (median two genes/patient, range 1-4). All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of two months (range 0.6-9.6) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1/130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. Monitoring of SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate molecular MRD monitoring in the majority of patients without a leukemia-specific target.
Copyright © 2021. Published by Elsevier Inc.