Myelodysplastic syndrome (MDS) is recognized as a preleukaemic disorder with a variable risk of transformation to acute myeloid leukaemia. Usually the blast cells in leukaemia are transformed after MDS displays a myeloid phenotype. Even though lymphoid progression had been reported previously, most displayed myeloid-lymphoid hybrid or early B phenotype. We report a case of an elderly man who had MDS transformed into Acute Lymphoblastic Leukaemia (ALL:L3) which is a rare lymphoid transformation.
In Malaysia, alpha-thalassaemia, beta-thalassaemia, haemoglobin (Hb) E, deltabeta-thalassaemia and Hb Constant Spring are prevalent. It has been estimated that 1 in 4 persons carries one of the above genetic abnormalities. In clinical practice, the major problems are: Hb Bart's hydrops fetalis (homozygous alpha(o)thalassaemia), homozygous 3(o)-thalassaemia, E-alpha thalassaemia and HbH disease. The laboratory procedures for diagnosis are standardised and the molecular basis of most of these genetic abnormalities are characterised. Thus it is possible to formulate a strategy for the detection and prevention of these disorders. The steps include the setting-up of population screening and genetic counselling service for the affected individuals, Society of Thalassaemias for public education and group support, and prenatal diagnosis with selective abortion of affected pregnancies. We embarked on such a programme between 1988 and 1992 in Kuala Lumpur General Hospital and hope to kindle similar effort in other state hospitals.
A system for computerising full blood picture reporting developed in-house using dBASE IV on IBM-compatible microcomputers in a local area network environment is described. The software package has a user-friendly interface which consists of a horizontal main menu bar with associated pull-down submenus. The package captures data directly from an automatic blood cell counter and provides options to modify or delete records, search for records, print interim, final or cumulative reports, record differential counts with an emulator, facilitate house-keeping activities which include backing-up databases and repairing corrupted indices. The implementation of this system has helped to improve the efficiency of reporting full blood picture in the haematology laboratory.
Myelodysplastic syndromes appear to be a rare group of blood disorders in Malaysia. It usually affects the elderly and some of the cases were reported to evolve into acute leukemia. We describe our experience with five cases, seen and managed by us over a 5-year period. All patients receiving supportive therapy died with one of them definitely known to transform to acute leukemia. The patient who survives till the time of writing received low dose continuous cytosine arabinoside infusion.
Residual disease in patients with acute leukaemia indicates unfavorable prognosis. The evaluation of remission using flow cytometry allows a better estimation of minimal residual disease (MRD) after induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL) cases. Patients in morphological marrow remission with presence of blast cells of less than 5%, may still have up to 1010 leukaemic cells. However with flow cytometric analysis, lower levels of the residual leukaemic cells (1 in 104 cells) can be detected and it can be used as a tool to predict relapse. This study compared the presenting clinical and haematological features of children with ALL and their residual disease status determined by flow cytometry. Analysis of their MRD status following remission-induction chemotherapy were done at day-28, week-12 and week-20. The cases were also followed up to five years, to determine their survival status. Their residual disease status by flow cytometric immunophenotyping was also compared with their bone marrow findings morphologically. Thirty-eight cases of precursor B-ALL in pediatric patients from UKM Medical Centre (UKMMC) were analyzed. There was no significant correlation between demographic, clinical and haematological features with MRD status at day-28. However, there was a significant correlation between MRD status by flow cytometry and by morphological marrow examination at week-12. Three cases showed persistent MRD findings until week-20 where two of the cases relapsed and died subsequently. Twenty four patients were still alive after five years of follow up.
Induced pluripotent stem cells (iPSC) are derived from human somatic cells through ectopic expression of transcription factors. This landmark discovery has been considered as a major development towards patient-specific iPSC for various biomedical applications. Unlimited self renewal capacity, pluripotency and ease of accessibility to donor tissues contribute to the versatility of iPSC. The therapeutic potential of iPSC in regenerative medicine, cell-based therapy, disease modelling and drug discovery is indeed very promising. Continuous progress in iPSC technology provides clearer understanding of disease pathogenesis and ultimately new optimism in developing treatment or cure for human diseases.
Owing to the importance of dendritic cells (DC) in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review surveys the heterogeneity of DC with regards to their phenotype and developmental origin, and how they initiate, modify and regulate the immune response, with emphasis on their maturation, migration, antigen-presentation and interaction with T cells and other immune cells. Much of this knowledge is obtained through research on murine DC. Research on human DC has been hampered by limitations associated with in vitro assays and limited access to human tissues. New approaches on human DC research are required in order to develop novel strategies for the treatment of microbial infections, the control of graft rejection, and the improvement of DC-based immunotherapeutic protocols for autoimmunity, allergy, and cancer.
Although there have been many new developments in the treatment of leukaemia with the use of new anti-leukaemic agents and stem cell transplantation, drug resistance and treatment failure remain a great challenge for the attending physician. Several studies have suggested that leukaemic stem cells (LSCs) play a pivotal role in chemoresistance and metastasis and the mechanisms by which these cells do so have also been elucidated. There is increasing evidence to show that there exists a large pool of therapeutic targets in LSCs and that the eradication of these cells is feasible with some promising results. This article gives an overview of different types of cancer stem cells (CSCs) derived from various types of leukaemia, the mechanisms by which LSCs contribute to drug resistance and metastasis and some recent advances in targeted therapy against LSCs.
Several fixation and permeabilization techniques that enable the flow cytometric analysis of the cell contents have been introduced in recent years. These methods allow sensitive detection of intracellular antigens that facilitates the diagnosis of certain diseases. We have undertaken in this study to evaluate a simple method of fixation and permeabilization using 2% paraformaldehyde and Tween 20. Intracellular antigens in three different leukaemia cases were analysed. We found that the method was reliable and easy. Intracellular kappa light chains were found in abundance in a case of plasma cell leukaemia. CD3 and CD22 were found in greater amount intracellularly than on the surface in pre-T-ALL and pre-pre B-ALL respectively.
A system for computerising histopathology records developed in-house using dBASE IV on IBM-compatible microcomputers in a local area network is described. The software package uses a horizontal main menu bar with associated pull-down submenus as interface between the machine and the user. It is very easy to use. The package provides options for selecting databases by years, entering/editing records, browsing data, making multi-characteristics searches/retrievals, printing data, and maintaining databases that includes backing-up and repairing corrupted databases.
A female Malay patient with acute lymphoblastic leukemia in remission for one year developed bilateral visual loss. The ophthalmoscopic appearance showed infiltration of optic nerves and retinae by leukemic cells. At that time, her blood, bone marrow and cerebral spinal fluid remained normal. She had received prophylactic cranial irradiation and intrathecal methotrexate as part of the treatment programme. It was likely therefore she had a leukemic relapse from a pharmacologic sanctuary in the eyes. She responded to local irradiation but did not regain her sight. Three months later, she had a bone marrow relapse.
The routine study of bone marrow trephine biopsies involves fixation, decalcification, paraffin-embedment, sectioning and staining. However, this process creates artifacts, produces shrinkage of tissue, consumes time and can result in sections of unsatisfactory cytological quality. It also renders the tissue unsuitable for enzyme-histochemical and immunohistochemical analyses. Frozen section of bone marrow without decalcification was evaluated as an alternative method for the study of bone marrow. This method was found to give sections with comparable cytological quality to that of paraffin-embedment, yielded sections for interpretation within 24 hours, and allowed enzyme-histochemical and immunohistochemical analyses to be applied successfully.
A 26-year-old assistant nurse suffered from acute lymphoblastic leukemia and was successfully treated with combination chemotherapy. 15 months later, she relapsed with a lump in her right breast. The significance of this finding is discussed.
The commonest cause of dementia among the elderly population is Alzheimer's disease (AD). It is a health concern globally as the number of people affected by dementia worldwide is rapidly increasing. Several genes have been linked to AD and the pathogenesis of the disease has been extensively and vigorously examined. Thus far, only a few drugs have been approved by the Food and Drug Administration (FDA) for the pharmacological treatment of AD and a growing body of research has turned to alternative options such as stem cell therapy. This review will give an overview of the pathological and clinical aspects of AD. Although researchers have explored the suitability and feasibility of using various types of stems cells to treat AD, this review will focus mainly on neural stem cells (NSCs)/ neural progenitor cells (NPCs). The behaviour and properties of NSCs will be described, accompanied by a comprehensive discussion of the therapeutic strategies involving the use of NSCs/NPCs in the treatment of the disease.
Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the deposition of amorphous non-congophilic materials predominantly in the kidneys leading to nephrotic syndrome or renal failure. As with light chain amyloidosis. MIDD is associated with a paraproteinemia. We report a patient suffering from multiple myeloma with IgG kappa paraproteinemia and immunoglobulin deposits predominantly in the bone marrow. The deposits are both as amorphous non-congophilic materials, and in the form of crystals, an observation not reported before.
A case of signet-ring cell lymphoma diagnosed initially by fine needle aspiration cytology is reported. This rare tumor is a variant of follicular lymphoma, which closely resembles metastatic adenocarcinoma and other tumors which exhibit signet-ring cell appearance. Correct diagnosis can be achieved by careful morphologic analysis together with positive reactivity with lymphoid markers. The cytohistologic, immunohistochemical and electron microscopic features are described, and the differ ential diagnostic considerations are discussed in the report.
Tissue Factor (TF) is a low molecular weight transmembrane glycoprotein that initiates the clotting protease cascade. It is considered to be the principal regulator of the extrinsic coagulation pathway, hemostasis and thrombosis, as well as inflammation and cellular immune response. An in-house two-step direct sandwich ELISA (enzyme-linked immunosorbent assay) for immunological quantification of plasma TF was successfully developed. The assay employed a monoclonal antibody against human TF (1:400 dilution; 1250 ng/ml) and peroxidase-conjugated anti-TF IgG (1:1000 dilution; 2000 ng/ml) as capture and detecting antibodies respectively, whilst tetramethylbenzidine/H2O2 were utilized as substrates. Titration curves of recombinant TF were linear within 10 to 4000 pg/ml, with a detection limit of 36.31 pg/ml. It demonstrated low intra- (2.50 - 9.23 CV%) and inter-assays (5.65 - 13.57 CV%) variability, as well as satisfactory analytical recovery (91.55 - 103.95%) and good parallelism. The assay developed was intended to be applied for measurement of plasma TF levels in patients with thrombotic disorders.