Hyperleucocytosis grading score and NPM1 gene mutation among patients with acute myeloid leukemia: Malaysian experience

Abstract

This is the first study evaluating the frequencies of nucleophosmin (NPM1) gene mutation according to the hyperleukocytosis (HL) grading score. The current two cut off values of this score in acute myeloid leukaemia (AML) patients are [1] those with 50-100 × 10 9 /L and [2] those with ≥ 100 × 10 9 /L total WBC count. The score represents the current clinically based definition of HL in patients with AML. A total of 90 patients with AML were included. AML patients were stratified into three groups: [1] those with a WBC count below 50 × 10 9 /L (n = 33), [2] those with a WBC count 50-100 × 10 9 /L (n = 29) and [3] those with a WBC above 100 × 10 9 /L (n = 28). Complete blood cell count, immunophenotyping and PCR of the exon 12 of NPM1 gene followed by sequencing analysis were done. NPM1 mutations were detected in 20/90 (22.2%) of patients with AML involving exon 12 of NPM1 gene and showed significant correlations with some hematologic characteristics. Contrary to expectation, no statistically significant difference was found in the WBC counts according to the NPM1 gene the mutation status among the studied groups. Also, there were no significant differences in the WHO classification categories according to the HL grading score. The difference in the frequency of NPM1 mutation in Asian compared to Western patients might be attributed to biology and aetiology variation of the disease in different population. The current two cut off values defining the HL are molecularly unreliable in spite of being clinically defined.

Detection of FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) Mutations from Marrow Tissues in Patients with Acute Myeloid Leukaemia

“…They also reported significantly higher platelet count and bone marrow blast percentage in patients without the NPM1 mutation. 21 NPM1 and FLT3 mutations are among the most frequently recurring molecular genetic changes in AML, predominantly in cytogenetically normal AML. 3,25,26 We, however, did not find any significant association between the cytogenetic results and these mutations.…”