1.Dismal outcome of therapy-related myeloid neoplasm associated with complex aberrant karyotypes and monosomal karyotype: a case report
Tang Yee-Loong’ Chia Wai-Kit ; Yap Ernie Cornelius Sze-Wai ; Julia Mohd Idris ; Leong Chooi-Fun ; Salwati Shuib ; Wong Chieh-Lee
The Malaysian Journal of Pathology 2016;38(3):315-319
Introduction: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated
myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in
stratifying patients into different risk groups and thus predict the response to treatment and overall
survival. Case report: A 59-year-old man was diagnosed with acute promyelocytic leukaemia.
Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved
remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and
ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He
achieved a second remission for the next 11 years. During a follow-up later, his full blood picture
showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed
hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence
in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result
revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related
myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was
made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia
in less than four months, complicated with severe pneumonia. Despite aggressive treatment with
antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.
Discussion and Conclusion: Diagnosis of t-MN should be suspected in patients with a history of
receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition
to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to
address the optimal management for patients with t-MN.
2.Plasma-Derived Microparticles in Polycythaemia Vera
Madzlifah AHADON ; Suria Abdul AZIZ ; Chieh Lee WONG ; Chooi Fun LEONG
The Malaysian Journal of Pathology 2018;40(1):41-48
Introduction: Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. Methods: A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. Results: Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). Conclusion: The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.
3.From Driver Mutations to Genomic Classification: Current & Future Perspectives on Myeloproliferative Neoplasms
Jaymi Tan ; Yock Ping Chow ; Norziha Zainul Abidin ; Abhi Veerakumarasivam ; Chieh Lee Wong
Malaysian Journal of Medicine and Health Sciences 2021;17(No.1):170-183
Myeloproliferative neoplasms (MPNs) encompass a heterogeneous group of chronic, clonal haematopoietic stem
cell neoplasms that harbor the propensity to undergo leukaemic transformation. Epidemiological data on MPNs
especially pertaining to non-Caucasian populations is limited, and the molecular pathogenesis of MPN remains
unclear. Although the discovery of MPN driver mutations in JAK2, MPL and CALR in the last decade has revolutionised disease management, the mutations are not specific for any MPN subtype. The management of MPNs is further
challenged by substantial genetic and phenotypic heterogeneity that exist between and within MPN subtypes as well
as other myeloid diseases. In this review, we focus on the classical Philadelphia chromosome (Ph)-negative MPNs –
polycythaemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF); providing an overview
on the current understanding of the disease at a clinical and molecular standpoint while discussing the present challenges and future opportunities in the management of MPNs.