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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 × 109/L and [2] those with ≥ 100 × 109/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 × 109/L (n = 33), [2] those with a WBC count 50–100 × 109/L (n = 29) and [3] those with a WBC above 100 × 109/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.

Effective prevention of β-thalassemia (β-thal) requires strategies to detect at-risk couples. This is the first study attempting to assess the prevalence of silent β-thal carriers in the Malaysian population. Hematological and clinical parameters were evaluated in healthy blood donors and patients with β-thal trait, Hb E (HBB: c.79G>A)/β-thal and β-thal major (β-TM). β-Globin gene sequencing was carried out for 52 healthy blood donors, 48 patients with Hb E/β-thal, 34 patients with β-TM and 38 patients with β-thal trait. The prevalence of silent β-thal carrier phenotypes found in 25.0% of healthy Malaysian blood donors indicates the need for clinician's awareness of this type in evaluating β-thal in Malaysia. Patients with β-TM present at a significantly younger age at initial diagnosis and require more blood transfusions compared to those with Hb E/β-thal. The time at which genomic DNA was extracted after blood collection, particularly from patients with β-TM and Hb E/β-thal, was found to be an important determinant of the quality of the results of the β-globin sequencing. Public education and communication campaigns are recommended as apparently healthy individuals have few or no symptoms and normal or borderline hematological parameters. β-Globin gene mutation characterization and screening for silent β-thal carriers in regions prevalent with β-thal are recommended to develop more effective genetic counseling and management of β-thal.

This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome. Keywords: Anaemia, Thalassemia, Mass spectrometry, Globin chain, Quantification, HPLC, Unknown peaks