Genetic polymorphisms of human platelet antigens-1 to -6, and -15 in the Malaysian population

BACKGROUND: Human platelet antigens (HPA) are determinant in several platelet-specific alloimmune disorders, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura and platelet transfusion refractoriness. The distribution of HPA systems in the Malaysian population is not known. Defining the patterns of HPA systems provides a basis for risk assessment and management of the above complications. MATERIALS AND METHODS: The aim of this study was to investigate the distribution of HPA -1 to -6 and -15 in the three major ethnic groups (Malay, Chinese and Indian) in the Malaysian population. A total of 600 random donor samples, 200 from each of the three ethnic groups, were genotyped by means of real time polymerase chain reaction (PCR) with hydrolysis probes and PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The most common genotype observed in this study was HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b (17%) followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b (14.33%). The allele frequencies of HPA in Malays and Chinese were found to be similar those of other East and South-East Asian populations, while those of Indians were comparable to the frequencies found in Europeans. CONCLUSION: The results of this study have been useful for determining the distribution of HPA polymorphisms in this region and for potential clinical implication

RBC-Y/MCV as a discriminant function for differentiating carriers of thalassaemia and HbE from iron deficiency

P>Individuals with alpha-thalassaemia (ATT), beta-thalassaemia (BTT) and HbE trait (HET) are often initially identified based on haematological parameters. However, the values of these parameters usually overlap with iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). We evaluated the use of RBC-Y in 156 normal individuals and 332 patients; ATT (n = 37), BTT (n = 61), HET (n = 25), HbH disease (n = 5), ACD (n = 67), IDA (n = 83) and ACD with IDA (n = 54). Diagnostic efficiency was analysed by receiver operating characteristics (ROC). MCH was better compared with RBC-Y in discriminating normal from abnormal with sensitivity and specificity of 94% at a cut-off of 26 pg. The Green and King (G&K) index performed the best in discriminating carriers from IDA and ACD with area under the ROC curve (AUCROC) of 0.81. However, if ACD was excluded, RBC-Y/MCV was a good discriminator for carriers from IDA with AUCROC = 0.845. In general screening of populations with ATT, BTT and HET, we propose that hypochromic individuals be first identified by MCH < 26 pg and carriers distinguished within these hypochromic individuals from IDA by using RBC-Y/MCV. However, if the prevalence of ACD were high within the screening population, G&K index would be a more suitable discriminator

The utility of immature reticulocyte fraction as an indicator of erythropoietic response to altitude training in elite cyclists

P>Altitude training is sometimes employed by elite endurance athletes to improve their sea level performance. This improvement results from the increased red cell mass consequent upon the boost in erythropoietin (EPO) level that occurs as a response to the relatively hypoxic environment at high altitudes. We measured serum EPO levels together with various red cell and reticulocyte parameters including immature reticulocyte fraction (IRF) in eight national track-endurance cyclists, resident at sea-level, prior to and upon return from an altitude of approximately 1905 m. Reticulocytes and soluble transferrin receptor (sTfR) were significantly increased with reduction in ferritin levels immediately on return from high altitude indicating increased erythropoietic activity. IRF in particular showed a significant peak immediately on return but decline to sub-baseline levels by day 9, and recovery to baseline by day 16. Our results indicate that IRF is a sensitive marker of erythropoietic status in athletes undergoing altitude training and subsequent loss of EPO stimuli on return to sea level

Imatinib resistance and blast transformation of chronic myeloid leukemia associated with a novel tri-nucleotide insertion mutation of BCR-ABL kinase domain at position K294

A letter to the editor is presented which discusses the introduction of imatinib mesylate (IM) in the medical case of an 18-year old man with in-frame mutations and blast transformation of chronic myeloid leukemia (CML)

A man with concomitant polycythaemia vera and chronic myeloid leukemia: the dynamics of the two disorders

The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is uncommon. We report a 60-year-old man who initially presented with phenotype of polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL fusion transcripts were detected in the initial sample. However, JAK2 V617F alleles diminished when BCR-ABL mRNA burden increased and reappeared once the patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only achieving clonal dominance when BCR-ABL positive clones are suppressed by imatinib

Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate

The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response

Myeloid Sarcoma: An Unusual Presentation of Acute Promyelocytic Leukemia Causing Spinal Cord Compression

Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted

Vox Sanguinis International forum on the selection and preparation of blood components for intrauterine transfusion.

Research into fetal development and medicin

A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer

10.1038/nm.2713Nature Medicine184521-528NAME