MATERIALS & METHODS: In total 141 local series of DLBCL cases from UKM Medical Centre were retrospectively studied.
RESULTS: Of these cases, we classified our patients into two subtypes: 32.7% (37/113) GCB and non-GCB 67.3% (76/113) by Hans algorithm and the results showed strong agreement with the results by Choi algorithm (κ = 0.828, P<0.001). Survival analysis indicated significant difference in between GCB and non-GCB subtypes (P=0.01), elevated serum LDH (P=0.016), age more than 60-year-old (P=0.021) and the presence of B symptoms (P=0.04). We observed 12% DLBCL cases were CD5 positive and 81.8% of them died of the disease (P=0.076). Analysis on the dual expression of MYC/BCL2 revealed that there is no significant difference in DE and non-DE groups (P=0.916). FISH study reported there were 9.22% (13/141) rearranged cases observed in our population at which highest frequency of BCL6 gene rearrangement (76.9%), followed by MYC (15.4%) and BCL2 (7.7%); no BCL10 and MALT-1 gene rearrangement found regardless of using TMAs or whole tissue samples. More cases of MYC protein overexpression observed compared to MYC translocation.
CONCLUSION: Relatively lower frequency of GCB tumours and low gene rearrangement rates were observed in Malaysian population. A national study is therefore warranted to know better the immunogenotypic characteristics of DLBCL in Malaysia and their implications on the survival.
CASE REPORT: Here we report a case of a 39-year-old lady, with an incidental finding of hyperleukocytosis (white blood cells count: 139.2 x 109/L). Her peripheral blood film revealed 36% of blasts and a bone marrow aspiration showed 53% of blasts. Immunophenotyping showed a population of blasts exhibiting positivity of two lineages, myeloid lineage and B-lymphoid lineage with strong positivity of CD34 and terminal deoxynucleotidyl transferase (Tdt). A conventional karyotyping revealed the presence of Philadelphia chromosome. She was diagnosed with MPAL with t(9,22), BCR ABL1, which carried a poor prognosis. She was treated with acute lymphoblastic leukaemia (ALL) chemotherapy protocol coupled with a tyrosine kinase inhibitor and was planned for an allogeneic stem cells transplant.
CONCLUSION: This MPAL case was diagnosed incidentally in an asymptomatic patient during medical check-up. We highlight this rare case report to raise the awareness about this rare disease. Understanding the pathogenesis of the disease with the underlying genes responsible for triggering the disease, uniform protocols for diagnosis and targeted treatment will help for proper management of these patients.
CASE REPORT: Her peripheral smear and bone marrow aspirate showed many myeloblasts. Chromosomal study revealed t(8;22;21)(q22;q12;q22) and loss of X chromosome. Fluorescence in situ hybridization (FISH) using whole chromosome painting probes confirmed the three-way translocation involving chromosomes 8, 21 and 22. RUNX1-RUNX1T1 rearrangement was identified in FISH and reverse transcriptase polymerase chain reaction confirming the diagnosis of AML with variant t(8;21). The patient was treated with standard chemotherapy. She achieved morphological remission one month after induction chemotherapy.
DISCUSSION: Although the clinical significance of variant t(8;21) is not well delineated, the evaluation of 31 such cases suggests patients with variant t(8;21) have similar prognosis to those with classical t(8;21).
METHODOLOGY: Cytokines and transcription factors in haematopoiesis and leukaemic mechanisms are described. Genetic features and clinical implications due to the encoded chimeric neoproteins causing malignant haematopoietic disorders are reviewed.
RESULTS AND DISCUSSION: Multiple translocation partner genes are well known for leukaemia such as MYC, MLL, RARA, ALK, and RUNX1. With the advent of more sophisticated diagnostic tools and bioinformatics algorithms, an exponential growth in fusion genes discoveries is likely to increase.
CONCLUSION: Demonstration of fusion genes and their specific translocation breakpoints in malignant haematological disorders are crucial for understanding the molecular pathogenesis and clinical phenotype of cancer, determining prognostic indexes and therapeutic responses, and monitoring residual disease and relapse status.
MATERIALS AND METHODS: CML patients on tyrosine kinase inhibitor (TKI) therapy and on regular follow up at University Kebangsaan Malaysia Medical Center (UKMMC) were selected. A comparative study was conducted between FISH and QRT-PCR for BCR-ABL transcripts at diagnosis and during follow-up.
RESULTS: There was good correlation between FISH and QRT-PCR for BCR-ABL. At 6th month of follow-up post diagnosis, FISH had a sensitivity of 83.3% and specificity of 65.2% (k >0.339, p<0.033). At 12th month, the sensitivity of FISH was 83% and the specificity was 59.1% (k >0.286, p <0.065). Similarly, at the 24th month, FISH had a sensitivity of 100% and specificity of 68.8% (k >0.642, p<0.000).
DISCUSSION: Early achievement of major molecular response (MMR) and complete cytogenetic remission (CCyR) were reliable predictors of long-term maintenance of molecular remission.
METHODOLOGY: Representative paraffin blocks of synovial sarcoma were utilized in this study. FISH study was performed on formalin-fixed paraffin embedded tissue sections using the SYT-SSX break apart probe from Cytocell, to detect two form of SYT-SSX transcript, SYT-SSX1 and SYT-SSX2. FISH protocol, including the hybridization was done following two different protocols, Cytocell FISH protocol and Optimized Dako FISH protocol.
RESULTS: Tissue samples subjected to FISH using Cytocell FISH protocol showed the absence of signal corresponding to the probe used. Utilizing Optimized Dako FISH protocol, the two signals (red and green) corresponding to the break-apart probes was detected. These findings suggested that Optimised Dako FISH protocol is more suited for use with the tested probe on paraffin embedded tissues in comparison to Cytocell FISH protocol.
CONCLUSION: Optimised Dako FISH protocol was noted to be more suited for detecting SYT-SSX FISH signals on paraffin embedded tissues in comparison to Cytocell FISH protocol.