Clinical and Hematological Profile of Nucleophosmin 1-Mutated Acute Myeloid Leukemia Compared with NPM1 Wild-Type Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Nucleophosmin 1 (NPM1) mutation, the commonest genetic lesion in adult acute myeloid leukemia (AML), defines a distinct entity, but its presenting profile has been described only in single cohorts.

Objective: To quantify how the presenting features of NPM1-mutated AML differ from those of NPM1 wild-type AML.

Methods: PubMed/MEDLINE, Europe PMC, OpenAlex and Scopus were searched for cohorts reporting presenting features by NPM1 status. Standardized mean differences (SMD) and odds ratios (OR) were pooled with random-effects models, and certainty was rated with GRADE. The primary outcome was white blood cell (WBC) count.

Results: Twenty-eight studies (7,126 patients; 1,747 NPM1-mutated) from nineteen countries were included. The WBC count difference was small and compatible with none (SMD 0.15 (95% CI −0.02 to 0.33); 11 studies; I² 27.6%; low certainty). NPM1-mutated AML had higher marrow blast percentages (SMD 0.50 (0.15 to 0.84)) and higher odds of female sex (OR 1.56 (1.39 to 1.77)), FAB M4/M5 morphology (2.21 (1.27 to 3.84)), FLT3-ITD (2.78 (1.89 to 4.08)) and normal karyotype (7.14 (3.97 to 12.83)), and lower odds of CD34 positivity (0.24 (0.13 to 0.46)). Certainty was moderate for sex and karyotype and low or very low otherwise. Complete remission, a treatment-dependent outcome, was more frequent (OR 2.36 (1.40 to 3.98)).

Conclusion: NPM1-mutated AML presents more often in women, with monocytic morphology, CD34-negative blasts, normal karyotype and FLT3-ITD; any excess in WBC count is small and uncertain. These features may help prioritize NPM1 testing where molecular diagnostics are limited, but cannot replace it.