Genetic characterizastion of biphenotypic acute leukemia patients

There are many subtypes defined in relation to structural chromosomal changes, DNA copy number changes and mutations that play a central role in the development of acute leukemia. Today, with the advancement of genomic research, new genetic subgroups have been identified in leukemias. Biphenotypic acute leukemias (MPAL) is a rare type of leukemia in which blasts co-express both lymphoid and myeloid lineage specific markers. Risk classification is based on clinical or immunophenotypic characteristics of MPAL patients, but they are highly heterogeneous both genetically and phenotypically. The molecular classification of patients are insufficient and they show a poor prognosis. The difficulties in classifying MPALs, the lack of prospectively collected data on therapeutic outcomes and rare incidence of rate lead to uncertainty about the best treatment approach for patients. Therefore, there is a need for the existence of prognostic markers that can guide the treatment of MPAL patients. In this thesis project, based on the hypothesis that MPAL patients have a special genomic background, candidate gene variations were investigated in bone marrow samples of 46 childhood MPAL cases using PCR, qPCR, Sanger sequencing approaches and informatics analysis. The relationship of the detected variations with the clinical parameters of the patients were investigated. In this study, we detected variations at least one of the IKZF1, DUX4r, ZNF384r, t(9;22) and t(12;21) in 39% (18/46) of the MPAL patients. Ectopic expression of transcription factors responsible for lineage commitment in hematopoietic cells have begun to be reported in MPAL patients. When the expressions of genes that have critical importance in the lineage change process are examined, no specific expression is observed for MPAL subgroups but it has been shown that the variations of MPAL patients affect and change gene expressions by direct or indirect mechanisms. The number of studies conducted in MPAL are negligible. Most of the data obtained in this thesis project are original data that have been revealed for the first time and differences from BCP-ALL were observed in terms of the frequency and co-occurrence of gene variations. The present work was supported by the Research Fund of Istanbul University. Project No. 36661