Myeloid Neoplasms With Erythroid Predominance and Excess Blasts in Young Adults Exhibit Distinct Genetic Profiles

Abstract

The evolution of acute myeloid leukemia (AML) classifications has progressively shifted the diagnostic focus toward genetic criteria. Nevertheless, morphology remains a key element in clinical practice, often serving as the initial trigger for additional molecular investigations. The diagnosis of acute erythroleukemia (AEML), initially defined by the FAB group, is no longer recognized as a distinct entity in the latest WHO and ICC classifications. Some studies have indicated that AEML shares similarities with myelodysplastic neoplasms, including a high frequency of TP53 mutations and adverse karyotypes. Here, we conducted a retrospective analysis in adults with AEML defined using historical morphologic criteria (≥ 50% erythroid precursors and ≥ 20% blasts among non-erythroid cells). In contrast to older patients, young adults (18-60 years) exhibit unique genetic profiles including a high prevalence of normal karyotypes (65%), NPM1 (35%) and UBTF (23%) mutations. AEML morphology in NPM1-mutated cases did not impact clinical outcomes but was associated with specific molecular features, including an enrichment of WT1 and cohesin gene mutations. In this age group, our findings support that morphologically defined AEML often corresponds to AML according to current genetic criteria, consistent with recent classification systems that prioritize molecular features over morphology.

Keywords: AML; NPM1; UBTF; classification; erythroleukemia.

FIGURE 1

AEML in young adults (18–60 years). (A) Classification of the AEML patients according to ICC 2022 and WHO criteria (n = 41 patients for whom data were available) The categories of AML in the ICC and WHO classifications are colored grey. MDS or MDS/AML categories (for ICC) are in white. (B) Molecular landscape (performed for n = 43 patients). RAS pathway: NRAS, KRAS, PTPN11, RIT1, CBL; Cohesin: RAD21, SMC1A, SMC3, STAG2; Spliceosome: SF3B1, SRSF2, U2AF1, ZRSR2. (C) Disease‐free survival and (D) overall survival according to the blast infiltration above (AML) or below (oligo‐AML) 20% among total BM nucleated cells (n = 41 patients receiving intensive chemotherapy for whom data were available).

FIGURE 2

AEML with NPM1 mutations in young adults. (A) May‐Grünwald‐Giemsa‐stained bone marrow smear in a 40‐year‐old female patient with NPM1 mutation (VAF 46%). The complete blood count showed pancytopenia (WBC 4.6 × 10⁹/L, hemoglobin 7.3 g/dL, platelets 89 × 10⁹/L). The bone marrow (performed twice with reproducible results) showed 6% myeloid blasts with erythroid hyperplasia (72% erythroblasts) and dysmyelopoiesis. (B) Pattern of co‐mutations in NPM1‐mutated AML according to the FAB subtype. (C) Disease‐free survival and (D) overall survival in AEML/M6‐FAB AML with NPM1 mutation compared to non‐M6‐FAB AML with NPM1 mutations.