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Chronic myeloid leukemia (CML) patients who have BCR-ABL T315I mutation, usually present in the advance phase of the disease with overall survival (OS) shorter than those without the mutation. This study aimed to determine the prevalence of T315I mutation amongst imatinib mesylate (IM) resistant CML patients and to compare the OS between T315I-mutated and non-T315I-mutated patients. Sixty consecutive CML patients who were treated with IM for at least 18 months and their treatment responses, were recorded. The mutation analysis was done using allele-specific oligonucleotide reverse transcriptase-polymerase chain reaction (RT-PCR) assay followed by direct sequencing technique. Forty-two patients (70%) were found to have IM-resistance. Five out of 42 patients had detectable T315I mutation. Median OS of IM-resistant T315I-mutated patients was 96 months (95% CI:54-138) compared to 84 months (95% CI:48-120) in non T315I-mutated patients, although this was found to be statistically insignificant (p = 0.43). The present study showed a higher prevalence of T315I mutation as compared to a few local studies. Median OS of T315I-mutated patients were observed to be longer than non-T315-mutated patients. Further studies encompassing larger cohort of patients are required to confirm this finding.

We present a case of a 61-year-old woman with relapse/refractory multiple myeloma post-autologous peripheral blood stem cell transplantation who presented with recurrent febrile episodes and infection. Worsening thrombocytopenia during lenalidomide-based therapy for early biochemical relapse warranted further investigations. Even though it was initially attributed to lenalidomide and relapse/refractory multiple myeloma, there was not much improvement in her counts despite adjustment of her medications. Subsequent serial bone marrow results and cytogenetic evolution eventually revealed therapy-related myelodysplastic syndrome progressing to therapy-related acute myeloid leukemia. In view of her age and comorbidities, she was treated with subcutaneous azacytidine with palliative intent which resulted in transient disappearance of blasts in the peripheral blood. She subsequently succumbed to progressive therapy-related acute myeloid leukemia and relapse/refractory multiple myeloma. This case highlights the complexity in diagnosing therapy-related myelodysplastic syndrome earlier as prompt diagnosis is crucial in delaying its progression to therapy-related acute myeloid leukemia. Managing therapy-related acute myeloid leukemia in the setting of relapse/refractory multiple myeloma post-autologous peripheral blood stem cell transplantation is challenging in terms of balancing the treatment toxicity and providing the best possible quality of life.

Background The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL. Methods “nCounter® Leukemia fusion gene expression assay” by NanoString was employed to detect various fusion transcripts in a large set samples (n = 94) utilizing RNA from formalin fixed paraffin embedded (FFPE) diagnostic bone marrow biopsy specimens. This series included AL patients with various recurrent translocations (n = 49), normal karyotype (n = 19), or complex karyotype (n = 21), as well as normal bone marrow samples (n = 5). Fusion gene expression data were compared with results obtained by conventional karyotype and FISH technology to determine sensitivity/specificity, as well as positive /negative predictive values. Results Junction probes for PML/RARA; RUNX1-RUNX1T1; BCR/ABL1 showed 100 % sensitivity/specificity. A high degree of correlation was noted for MLL/AF4 (85 sensitivity/100 specificity) and TCF3-PBX1 (75 % sensitivity/100 % specificity) probes. CBFB-MYH11 fusion probes showed moderate sensitivity (57 %) but high specificity (100 %). ETV6/RUNX1 displayed discordance between fusion transcript assay and FISH results as well as rare non-specific binding in AL samples with normal or complex cytogenetics. Conclusions Our study presents preliminary data with high correlation between fusion transcript detection by a throughput automated multiplexed platform, compared to conventional karyotype/FISH technique for detection of chromosomal translocations in AL patients. Our preliminary observations, mandates further vast validation studies to explore automated molecular platforms in diagnostic pathology. Electronic supplementary material The online version of this article (doi:10.1186/s13000-016-0541-z) contains supplementary material, which is available to authorized users.

Burkitt’s lymphoma (BL) continues to pose challenges in the human immunodeficiency virus ( HIV ) -infected population and may present at more advance stages with multiple areas of extranodal involvement. Other chromosomal abnormality in addition to the characteristic t (8 : 14) translocation also associated with poor outcome in BL. Here we report a case of an HIV seropositive adult male with the diagnosis of BL who presented with bone marrow and peripheral blood involvement of the disease. Cytogenetic analysis showed presence of complex chromosomal abnormality, with characteristic translocation of t (8 : 14) and an additional isochromosome 1q.

Chronic myeloid leukaemia (CML) is typically associated with reciprocal translocation between long arms of chromosome 9 and 22, t (9, 22) (q34; q11.2) and with the formation of a BCR-ABL fusion gene. In a minority of newly diagnosed CML cases, complex cytogenetic variants of the Ph chromosome can be observed with involvement of chromosomes 9, 22 and a third chromosome. Herein, we describe a lady with CML in chronic phase with a complex translocation involving chromosomes 9, 22 and 12. Conventional karyotyping revealed t (9, 12). Fluorescence in-situ hybridization (FISH) showed BCR-ABL fusion signals in 60% nucleated cells (cut-off levels ≥5% for positive signals). Whole chromosome painting (WCP) showed presence of a complex variant translocation between chromosomes 9, 12 and 22. However, DNA analysis for BCR-ABL fusion gene was negative. Cytoreductive therapy and Imatinib treatment were initiated.

The epileptic encephalopathies of infancy and childhood are a collection of epilepsy disorders characterized by refractory, severe seizures and poor neurological outcome, in which the mechanism of disease is poorly understood. We report the clinical presentation and evolution of epileptic encephalopathy in a patient, associated with a loss-of-function mutation in the phospholipase C-β 1 gene. We ascertained a consanguineous family containing a male infant who presented with early-onset epileptic encephalopathy for detailed clinical phenotyping and molecular genetic investigation. In addition, a cohort of 12 consanguineous families of children with infantile spasms were analysed for linkage to the phospholipase C-β 1 gene locus. The male infant presented with tonic seizures in early infancy and subsequently developed infantile spasms. Over time, he developed drug-resistant epilepsy associated with severe neurological regression and failure to thrive. Molecular genetic investigation revealed a homozygous loss-of-function 0.5-Mb deletion, encompassing the promoter element and exons 1, 2 and 3 of phospholipase C-β 1 in the index case. Linkage to the phospholipase C-β 1 locus was excluded in the 12 other consanguineous families, consistent with genetic heterogeneity in this disorder. Although phospholipase C-β 1 deficiency has not previously been reported in humans, the Plcb1 homozygote knockout mouse displays early-onset severe tonic seizures and growth retardation, thus recapitulating the human phenotype. Phospholipase C-β 1 has important functions in both hippocampal muscarinic acetylcholine receptor signalling and in cortical development. Thus, the discovery of a phospholipase C-β 1 mutation allows us to propose a novel potential underlying mechanism in early-onset epileptic encephalopathy.