Page 20 - Haematologica March 2020

Editorials
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Figure 1. The 17-gene leukemia stem cell score refines prognosis in acute myeloid leukemia beyond that afforded by the European LeukemiaNet risk categories.
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(A) Patients with acute myeloid leukemia (AML) with a 17-genelow leukemia stem cell (LSC) score more frequently have biallelic CEBPA, GATA2, and KIT mutations and are more sensitive to chemotherapy. (B) Patients with AML with a 17-genehigh LSC score more frequently have unfavorable molecular abnormalities and are more resistant to chemotherapy. (C) The 17-gene LSC score has a powerful prognostic impact, particularly in younger adult AML patients (aged <60 years).
A study by Ng et al. recently defined a list of genes dif- ferentially expressed between LSC and non-LSC fractions (validated by xenotransplantation) from 78 AML patients.7 The list of genes highly expressed in LSC was subjected to statistical regression analysis to relate the expression profile to patients’ survival, which yielded an optimal “17-gene LSC score” prognostic signature. When the scoring algorithm was applied to five cohorts of AML patients, high scores consistently correlated with poor prognostic factors such as older age, higher initial white blood cell count, and unfavorable cytogenetics. High scores also correlated with resistance to standard induc-
tion chemotherapy, higher rates of relapse, and poor out- comes including inability to achieve complete response, decreased overall survival, and shorter event-free and relapse-free survival. Ng et al. proposed that this scoring tool could be applied to guide selection of initial therapy in newly diagnosed patients, specifically to identify high- risk patients not likely to benefit from standard induction chemotherapy.
In this issue of Haematologica, Bill et al. provide an impressive validation of the 17-gene LSC scoring system using RNA-sequencing data from a large number of patients treated in cooperative group (CALGB) trials.8
haematologica | 2020; 105(3)