Chronic lymphocytic leukaemia trends and features at a tertiary hospital in South Africa (2011–2016)

Background: Chronic lymphocytic leukaemia (CLL) is a common lymphoproliferative disorder in developed countries. However, this condition is rare in Africa and there is a paucity of information on CLL, specifically on the continent.Aim: This study described, retrospectively, the frequency, demographics and laboratory features of CLL cases diagnosed from 2011 to 2016.Setting: Department of Pathology, National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town.Methods: A retrospective analysis was performed for all CLL diagnoses made between 01 January 2011 and 31 December 2016.Results: Eighty CLL cases were diagnosed between 2011 and 2016. Men and women presented with the disease equally (48.8% vs. 51.2%, p 0.05). The mean age at diagnosis was 66.79 years (range of 37–95 years) and the modal age range (36.3%) was 60–69 years. Men presented with the disease at a significantly younger age than women (mean = 64 years vs. mean = 69.5 years, p 0.05). There were three (3.75%) human immunodeficiency virus (HIV)-positive patients (age range 43–50 years). Chromosome 13q14 deletion was found in 6 out of 19 patients (31.6%). Trisomy 12 and deletion 11q22 were found in 5 out of 21 (24%) and 7 out of 21 (33.3%) patients, respectively. Deletions 13q34 and 17p were negative for 6 and 20 patients, respectively.Conclusion: Chronic lymphocytic leukaemia at our facility presented equally in men and women. Men presented with the disease at a younger age than women. Additionally, our findings suggested that HIV is uncommon amongst CLL patients tested for HIV.

Knockout of both miR-15/16 loci induces acute myeloid leukemia

MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16–1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16–1 and miR-15b/16–2 has been demonstrated to promote B cell malignancies. Here, we evaluate the biological role of miR-15/16 clusters, crossbreeding miR-15a/16–1 and miR-15b/16–2 knockout mice. Unexpectedly, the complete deletion of both clusters promoted myeloproliferative disorders in the majority of the mice by the age of 5 months with a penetrance of 70%. These mice showed a significant enlargement of spleen and abnormal swelling of lymph nodes. Flow cytometry characterization demonstrated an expanded CD11b/Gr-1 double-positive myeloid population both in spleen and in bone marrow. The transplantation of splenocytes harvested from double-KO mice into wild-type recipient mice resulted in the development of myeloproliferative disorders, as observed in the donors. In vivo, miR-15/16 cluster deletion up-regulated the expression of Cyclin D1, Cyclin D2, and Bcl-2. Taken together, our findings identify a driver oncogenic role for miR-15/16 cluster deletion in different leukocytic cell lineages.

Successful pregnancy in the context of previously undiagnosed chronic lymphocytic leukaemia: A case report and literature review

An asymptomatic 36-year-old woman presented with significantly elevated white blood cells (165.9 × 109/L) at antenatal booking, in her first pregnancy. Further investigations revealed the diagnosis of chronic lymphocytic leukaemia with monoallelic deletion of chromosome 13q14. She was supported and monitored through out pregnancy, without treatment, and delivered a healthy baby boy at term with no complications and is currently being followed up by the haem-oncology team.

A functional AT/G polymorphism in the 5′-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14

The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5′-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26 × 10−21). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2.

Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14

Introduction: Prostate cancer is the most frequent malignancy found to occur in Caucasian men, but its genetic basis remains elusive. A prostate cancer-susceptibility locus has been identified on chromosome 13q14. The tumour suppressor gene deleted in cancer cells 1 (DICE1/INTS6) is located within this interval on 13q14.3. Materials and Methods: We performed mutation analysis of the DICE1/INTS6 gene in thirteen German prostate cancer families. Results and Conclusion: None of the patients harboured DICE1 mutations, and similar frequencies of the previously identified 13 bp deletion polymorphism in the DICE1 promoter were observed in the familial prostate cancer patients as compared with sporadic prostate cancer patients and controls. However, in one family with three affected brothers, the variations c.1215A>C (p.T405T) in exon 10 and c.2568A>G (p.S856S) in exon 17 were detected in a heterozygous pattern. In sporadic prostate cancer patients, variant c.2568A>G (p.S856S) was detected in 10/325 (3.08%) compared with 5/207 (2.42%) control samples (p > 0.05). We conclude that DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.