Reference values for reticulocyte haemoglobin equivalent in healthy Chinese children under 5 years and its associations with various blood parameters.

Background: Reticulocyte haemoglobin equivalent (RET-He) is a useful tool for evaluating recent iron usage irrespective of inflammatory status. This study aims to establish a reference for RET-He among Hong Kong healthy children under the age of 5 years and to investigate the association between RET-He and various blood parameters.

Methods: A total of 946 children aged 2-48 months from July 2019 to December 2022 were recruited in this cross-sectional study.

Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine.

Unlabelled: Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models.

NGS4THAL, a One-Stop Molecular Diagnosis and Carrier Screening Tool for Thalassemia and Other Hemoglobinopathies by Next-Generation Sequencing.

Thalassemia is one of the most common genetic diseases and a major health threat worldwide. Accurate, efficient, and scalable analysis of next-generation sequencing (NGS) data is much needed for its molecular diagnosis and carrier screening. We developed NGS4THAL, a bioinformatics analysis pipeline analyzing NGS data to detect pathogenic variants for thalassemia and other hemoglobinopathies.

Congenital Hemolytic Anemia Because of Glucose Phosphate Isomerase Deficiency: Identification of 2 Novel Missense Mutations in the GPI Gene.

Glucose phosphate isomerase (GPI) deficiency is the second most common red blood cell enzymopathy involving the glycolysis pathway. It is an autosomal recessive disorder. Chronic hemolytic anemia is a common manifestation.

A molecular study on the role of alpha-hemoglobin-stabilizing protein in hemoglobin H disease.

The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely clear how genetic and environmental factors interplay to modify clinical severity in affected individuals. Previous studies suggested that altered structure or function of alpha-hemoglobin-stabilizing protein (AHSP) could modify the clinical phenotypes of thalassemias.

Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute myeloid leukemia.

An in vitro drug-screening platform on patient samples was developed and validated to design personalized treatment for relapsed/refractory acute myeloid leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine (HHT), also known as omacetaxine mepesuccinate, exhibited preferential antileukemia effect against AML carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to suppress leukemia growth in vitro and in xenograft mouse models.

Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms.

Aims: Megakaryocyte expansion in myeloproliferative neoplasms (MPNs) is due to uncontrolled proliferation accompanied by dysregulation of proapoptotic and antiapoptotic mechanisms. Here we have investigated the intrinsic and extrinsic apoptotic pathways of megakaryocytes in human MPNs to further define the mechanisms involved.

Methods: The megakaryocytic expression of proapoptotic caspase-8, caspase-9, Diablo, p53 and antiapoptotic survivin proteins was investigated in bone marrow specimens of the MPNs (n=145) and controls (n=15) using immunohistochemistry.

Curative Stem Cell Transplantation for Severe Hb H Disease Manifesting From Early Infancy: Phenotypic and Genotypic Analyses.

Most people with Hb H disease live normal lives; however, a minority of cases requires lifelong regular transfusions. An atypical form of nondeletional Hb H disease was reported in a Thai boy, characterized by severe persistent hemolytic anemia since the age of 2 months. Molecular diagnosis revealed the apparent compound heterozygosity for the Southeast Asian (- -(SEA)) and α2 polyadenylation (polyA) signal (AATAAA>AATA- -) deletions.

Genetic basis of persistent red blood cell microcytosis in the Chinese unexplained by phenotypical testing.

Aims: Hypochromic microcytic anaemia is the hallmark phenotype of thalassaemia. Current phenotypical tests do not provide a diagnosis in a small proportion of patients with red blood cell microcytosis. We aim to evaluate the genetic basis of red cell microcytosis in these cases in our Chinese population.

A comparison of high resolution melting, allele-specific priming and Sanger sequencing for the detection of BRAFV600E mutation in hairy cell leukaemia from different haematological specimens.

The BRAFV600E mutation is a highly sensitive and specific marker for the diagnosis of hairy cell leukaemia (HCL) and a potential therapeutic target. We assessed the performance of high resolution melting (HRM), allele-specific priming (ASP) and Sanger sequencing (SS) for BRAFV600E detection in 17 unenriched samples from 15 HCL patients: blood (n = 7), marrow aspirate (n = 3), ethylenediaminetetraacetic acid (EDTA)-decalcified trephine biopsy (n = 2), formic acid (FA)-decalcified trephine biopsy (n = 5). Our results showed that for blood and marrow aspirate samples, both HRM and ASP had a very high analytical sensitivity (1%) in clinical specimens and excellent diagnostic sensitivity (100%) and specificity (100%) in analysable samples.

Novel point mutation of the α2-globin gene (HBA2) and a rare 2.4 kb deletion of the α1-globin gene (HBA1), identified in two chinese patients with Hb H disease.

Two Chinese patients with mild and moderate Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2) in addition to the - -(SEA) deletion. One patient was a 41-year old man with mild anemia (Hb 11.3 g/dL).

Epigenetic inactivation of DAPK1, p14ARF, mir-34a and -34b/c in acute promyelocytic leukaemia.

Aim: TP53 mutation frequently occurs in solid cancers but not haematological cancers including acute promyelocytic leukaemia (APL) characterised by t(15;17). Both DAPK1 and p14(ARF) positively regulate p53 whereas miR-34a and -34b/c are direct transcriptional targets of p53. We studied if DNA methylation might contribute to inactivation of gene/microRNA (miRNA) in the TP53 tumour suppressor network.

Establishment of a bortezomib-resistant Chinese human multiple myeloma cell line: MMLAL.

Background: A new human myeloma cell line, MMLAL, was established from the myelomatous pleural effusion of a 73-year-old Chinese patient suffering from symptomatic International stage III IgG/lambda myeloma. After a brief period of complete remission, he developed aggressive systemic relapse complicated by malignant pleural effusion with exclusive plasma cell infiltration. His disease remained chemo-refractory, and died six months after relapse.

Diagnosis and prevention of thalassemia.

Thalassemia is the most common monogenic inherited disease worldwide and it affects most countries to various extents. This review summarizes the current approaches to phenotypic and genotypic diagnosis of thalassemia in clinical practice. Prevention strategies that encompass carrier screening, genetic counseling and prenatal diagnosis are discussed.

Epigenetic dysregulation of leukaemic HOX code in MLL-rearranged leukaemia mouse model.

HOX genes are frequently dysregulated in human leukaemia with the gene rearrangement between mixed lineage leukaemia (MLL) and partner genes. The resultant MLL fusion proteins are known to mediate leukaemia through disruption of the normal epigenetic regulation at the target gene loci. To elucidate the pathogenic role of MLL fusion proteins in HOX dysregulation in leukaemia, we generated a novel haematopoietic lineage-specific Mll-Een knock-in mouse model using a Cre-mediated inversion strategy.

Diagnostic challenges in a case of B cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) is a recently recognized category of mature B-cell lymphoma. This represents a heterogeneous group of diseases which often pose diagnostic problems in clinical practice, yet its distinction from DLBCL to BL is important for its therapeutic and prognostic implications. We report the challenging diagnostic process of a 60-year-old man.

Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7.

First reported case of prenatal diagnosis for pyruvate kinase deficiency in a Chinese family.

We describe the first case of prenatal diagnosis for pyruvate kinase (PK) deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with non-spherocytic hemolytic anemia. A Han Chinese child with a history of severe transfusion-dependent hemolytic anemia was diagnosed to have PK deficiency. Prenatal diagnosis was performed on the second child based on the genetic findings from the family.