Vynnytska O. Features of mutational status in childhood acute lymphoblastic leukemia

Modern molecular genetic diagnosis of acute lymphoblastic leukemia (ALL) is based on the identification of specific genetic disorders that are associated with malignant cell transformation. Genodiagnostics allows not only to analyze the degree of malignancy of the process, but also to conduct early identification of markers of unfavourable prognosis for the course of the disease, to conduct early diagnosis of relapses, largely remove the subjectivity factor in assessing a particular clinical syndrome, which is crucial for treatment tactics. The dissertation is devoted to the study of blast cell immunophenotyping, spectrum and expression of chimeric genes, changes in clinical and laboratory parameters in peripheral blood in comparison with the indicators of the course of childhood ALL. The role of markers of molecular genetic diagnosis of childhood ALL caused by disease and the effectiveness of cytostatic therapy ALLIC BFM-2009 was evaluated. The dissertation research shows the prognostic value and therapeutic strategy of chromosomal disorders during and after cytostatic therapy ALLIC BFM-2009, as well as in the case of relapse. Study shows that the presence of morphological remission in patients with ALL does not always indicate a complete reduction of the tumor clone. Molecular genetic features of blast cells underlie various methods of detecting a small number of tumor cells. These include the method of standard cytogenetics and immunofluorescence hybridization (monitoring of various chromosomal aberrations), flow cytofluorometry (detection of aberrant immunophenotype), the method of polymerase chain reaction (PCR) (determination of the expression of chimeric oncogenes). Detection of minimal residual disease (MRD) at different stages of therapy is a favorable prognostic factor for recurrence. Therefore, the use of tumor markers for monitoring significantly increases its reliability and prevents false negative results. For the first time, a comprehensive study of the immunophenotype of blast cells depending on the development of relapses and complete remission was conducted. Study of blast cell antigenic composition after ALLIC-BFM 2009 cytostatic therapy in patients with relapses showed a high level of immunophenotype of linearly independent lymphoblasts – expression of CD34, HLA, Auti-TdT, CD10 and CD38. The presence of the CD38 marker is not related to the clinical picture observed in ALL and does not affect the overall survival of patients. Expression of the myeloid markers CD33 and CD13 has been reported in patients with ALL, which has been linked to patient survival. The longer survival of patients with ALL was shown to correlate with the expression on CD13 blast cells, while the expression of CD33 on blast cells indicates low recurrence-free and eventless survival of patients with ALL The study confirms the existing opinion about the dependence of the disease on the presence of chromosomal translocations. Treatment in patients with and without translocations did not show changes in the mean leukocyte count (3g/L), whereas the maximum leukocyte count in patients with translocations was 38 g/L, and in patients without translocations – at levels of 102 g/L. Deviations in the number of leukocytes from the arithmetic mean are associated with the type of chromosomal aberration, as the highest fluctuations in the number of leukocytes in the blood are observed in patients with the BCR / ABL chimeric gene. In the work, based on the obtained data, the range of genetic criteria for predicting the course of the АLL disease and the development of relapses has been expanded. The optimal scheme of studies of genetic disorders in children with АLL has been improved.