Long noncoding RNA profiling may be effective for stratification in pediatric AML

From Hematology Advisor by Jonathan Goodman

A single-assay system that incorporates long noncoding RNA expression appears to effectively predict disease prognosis among pediatric patients with acute myeloid leukemia (AML), according to research published in the Journal of Clinical Oncology.

Genetic analysis has previously been used to better understand disease biology and etiology over the past 2 decades. In the pediatric AML setting, however, genomic analysis has not frequently been included in stratification programs.

In recent years, micro-RNA and long noncoding RNA have been included in overall gene profiling techniques, given research has suggested that altered long noncoding RNA expression may be involved in AML development and progression. For this retrospective study comprised of data from previous trials, researchers investigated the utility of including long noncoding RNA analysis in prognostic stratification in pediatric AML.

Data from 1298 pediatric patients were included; these included 780 patients in a training cohort, 260 patients in an initial validation cohort, and 258 patients in a second validation cohort. In the overall cohort, 51.4% of patients were male sex, 50.3% were between 3 and 14 years of age, and 73.5% had a complete remission after first induction treatment course.

The authors sequenced all training patient specimens. Using specimens where long noncoding RNA transcripts were upregulated, the authors developed a 37 long noncoding RNA signature, which they designated the lncScore.

Analysis of training set data suggested that positive lncScores corresponded to 5-year event-free survival and overall survival rates of 26.7% and 42.7%, respectively; these contrasted with 56.9% and 76.3%, respectively, found among patients with negative lncScores (hazard ratios, 2.48 and 3.16; <.001).

Similar findings were noted in the pediatric validation cohorts and an adult AML group. Further analysis suggested that lncScore was prognostically relevant in multivariate models and in heterogenous subgroups currently categorized as “intermediate risk.”

“The inclusion of lncScore, as a standalone assay, or in combination with other sequencing analyses, is fully compatible with a broader move toward next-generation sequencing as an upfront diagnostic modality in AML,” the authors claimed.

SourceHematology Advisor

Farrar JE, Smith JL, Othus M, et al. (2023) Long noncoding RNA expression independently predicts outcome in pediatric acute myeloid leukemia. J Clin Oncol [Epub ahead of print]. [article]

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