Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

BACKGROUND: Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. METHODS: The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. RESULTS: Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). CONCLUSIONS: The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

Increased risk of chronic lymphocytic leukaemia among cancer survivors in the Netherlands: increased detection, causal factors or both?

We assessed the risk of chronic lymphocytic leukaemia (CLL) following earlier primary malignancies (EPM) to explore the extent and determinants of this risk. We used the Netherlands Cancer Registry data of 1,313,232 cancer survivors who were at risk to be subsequently diagnosed with CLL between 1989 and 2008. Cancer survivors were categorized based on gender, age, time since diagnosis of EPM and type of EPM. CLL was regarded synchronous when diagnosed within 3 months after diagnosis of EPM; metachronous CLLs were those diagnosed later. Overall, we found that cancer survivors had a 90 % higher risk to be diagnosed with CLL than the general population. In the first year after diagnosis, we found a more than four-fold increased risk of CLL (standardized incidence ratio (SIR), 4.4; 95 % confidence interval (CI), 4.1-4.8); however, no increased risk was observed after excluding synchronous cases. After 1 year, the excess risk of subsequent CLL ranged from 1.2 to 1.8. An increased risk for metachronous CLL was found in prostate (SIR 1.3; 95 % CI 1.1-1.5) and squamous cell skin cancer survivors (SIR 2.3; 95 % CI 1.9-2.7). Intensive clinical checkups after/around diagnosis of the EPM seemed to be the main cause for the increased risk of CLL among cancer survivors. However, possible shared risk factors between prostate cancer and CLL and skin cancer and CLL cannot be excluded. Further clinical research aimed at CLL as subsequent primary malignancy (SPM) is warranted to elucidate possible shared biological and predisposing risk factors

MDS classification is improving in an era of the WHO 2016 criteria of MDS: A population-based analysis among 9159 MDS patients diagnosed in the Netherlands

Background Morphologic and cytogenetic assessments are required to characterize diagnostic and prognostic features of myelodysplastic syndromes (MDS). We assessed whether these assessments were performed among newly diagnosed MDS patients in the Netherlands. Methods MDS cases were retrieved from the nationwide Netherlands Cancer Registry (N = 9159; period 2001–2014) and the regional PHAROS MDS registry (N = 676; period 2008–2011). Results The proportion of unclassified MDS decreased from 58% in 2001 to 13% in 2014. Data from the more detailed PHAROS registry revealed that the degree of bone marrow dysplasia was only reported in ∼30% of all evaluable bone marrow aspirates. Further, the International Prognostic Scoring System was undetermined in 55% of patients, primarily owing to unperformed cytogenetics in 46% of patients. Conclusion The classification of MDS is improving in the Netherlands. Nevertheless, particular diagnostic and prognostic procedures that are essential for the diagnosis and subsequent treatment decision-making of MDS were not fully utilized in particular patient subsets