Identification of HLA alleles involved in immune thrombotic thrombocytopenic purpura patients from Turkey.

Thrombotic thrombocytopenic purpura (TTP) is one of the rare group disorders classified as thrombotic microangiopathies (TMAs). Approximately 90% of TTP developed immune-mediation by the formation of antibodies against the enzyme ADAMTS-13. The exact cause is unknown. To establish an association between human leukocyte antigen (HLA) and autoimmune basis, as susceptibility or protection against the disease, we contributed a study aiming to evaluate the role of HLA in immune-mediated TTP (iTTP). Considering epidemiological factors such as age, sex, ethnicity, and geographical origins, we contributed the study in our country, Turkey, which consist of a very heterogeneous population. Patients' data collection was retrospectively from electronic database on two University hospitals having big therapeutic apheresis service. Control arm was healthy people registered as stem cell donors matched in terms of age and sex. The frequency of HLA-DRB1 and HLA-DQB1 alleles between acquired TTP and the control group was compared using the chi-square method. Yates correction and logistic regression were performed on these results. A total of 75 iTTP patients and 150 healthy individuals enrolled to the study. HLA-DRB1∗11, HLA-DQB1∗03, HLA-DRB1∗11:01, HLA-DRB1∗14:01, HLA-DRB1∗13:05, HLA-DRB1∗11 + HLA-DQB1∗03 allele pair and HLA-DRB1∗15 + HLA- DQB1∗06 were proved to be susceptibility allele pairs for iTTP. HLA-DRB1∗15, HLA-DRB1∗01:01, HLA-DRB1∗07:01, HLA-DRB1∗13:01, HLA-DRB1∗14:54, HLA-DQB1∗05:01, HLA-DQB1∗02:02 and HLA-DRB1∗07 + HLA-DQB1∗02 allele pair were found to be protective against iTTP. Our findings support an association with iTTP across very heterogenous populations in Turkey.

Overview of clinical and genetic features of CML patients with variant Philadelphia translocations involving chromosome 7: A case series.

Variant Philadelphia (Ph) translocations involving chromosome 7 are rarely seen in Chronic Myeloid Leukemia (CML) patients. It is aimed to contribute new cases to the literature by reviewing the cases in our archive and shed light into the understanding of the role of chromosome 7 in CML. This study was carried out in 237 newly diagnosed CML patients with variant Ph translocations. Among the patients, those with variant Ph translocation involving chromosome 7 were evaluated in terms of clinical and genetic characteristics. Chromosome analysis was performed on 24 and 48 h of bone marrow cultures. FISH analysis was performed with BCR-ABL1 dual color dual fusion translocation probes. BCR-ABL1 transcript levels were analysed by QRT-PCR and results were reported as BCR-ABL1/ABL1 (BCR-ABL1 (IS) %) according to international scale. Four of the patients had variant Ph translocations including chromosome 7. The karyotypes were 46,XX,t(7;9;22)(p13;q34;q11); 46,XX,t(7;9;22)(p21;q34;q11); 46,XX,t(7;9;22)(q22;q34;q11) and 46,XY,t(7;9;22)(q22;q34;q11). The breakpoints demonstrated by cytogenetic analysis were confirmed by FISH analysis. Monitoring by QRT-PCR showed that patients with variant Ph translocation including 7p13 and 7p21 had a dramatic decrease in BCR-ABL1 levels resulting in complete hematological, complete cytogenetic and deep molecular responses. Despite achieving complete hematological, complete cytogenetic response in two patients with variant Philadelphia translocation, including 7q22, no major molecular response was achieved and both patients are still in the warning category. Response to tyrosine kinase inhibitör therapy may be associated with both the variant translocation mechanism and new gene interactions that occur due to the breakpoints of additional chromosomes involved in translocation.