PB1801: CHROMOSOMAL ABNORMALITIES DURING THE CLINICAL COURSE OF ADULT ACUTE MYELOID LEUKEMIA

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Background: Using conventional cytogenetics, an abnormal karyotype can be detected in 60-70% of adult acute myeloid leukemia (AML) patients. Taking into consideration the identified cytogenetic abnormalities AML patients are currently classified into three risk groups: favorable, intermediate and adverse. These genetic abnormalities are the most important factors in determining response to chemotherapy as well as outcome in AML. Aims: Aim of this study was to detect the diagnostic and prognostic significance of chromosomal abnormalities in leukemic cells at different phases of AML. Methods: Cytogenetic investigations of bone marrow and/or peripheral blood cells from 140 adult patients were performed during clinical evolution of AML: in newly diagnosed patients, in remission and at relapse. The methods of conventional cytogenetics (GTG) and fluorescence in situ hybridization (FISH) were used. Cytogenetic methods were performed using standard techniques and karyotypes were described according to the International System for Human Cytogenetic Nomenclature. Results: Cytogenetic investigations of 140 adult AML patients were performed in newly diagnosed patients, in remission and at relapse. Structural (del(5q), del(7q), rearrangements of 3q, 12p, 17p and 11q23, t(8;21)(q22;q22), t(9;22)(q34;q11), t(15;17)(q22;q21), t(16;16)(p13;q22), inv(16)(p13q22), marker and ring chromosomes, acentric structures and others) and numerical (-5, -7, -Y, +8, monosomal karyotype and others) chromosomal abnormalities in leukemic cells were found. Some genetic abnormalities (BCR/ABL1, PML/RARa, AML1/ETO, CBFβ/MYH11 fusion genes) were detected by molecular genetic methods (FISH). Spectrum of cytogenetic abnormalities had an important diagnostic and prognostic significance. Diagnosis of AML was possible due to the presence of specific genetic markers that can confirm some types of AML (AML with t(8;21)(q22;q22), t(9;22)(q34;q11), t(15;17)(q22;q21), t(16;16)(p13;q22)/inv(16)(p13q22), 3q21q26 rearrangements, BCR/ABL1, PML/RARa, AML1/ETO, CBFβ/MYH11 fusion genes). Taking into consideration the identified cytogenetic abnormalities AML patients were classified by risk groups: the group of patients with adverse cytogenetic markers (3q21q26 rearrangements, -5, -7, t(9;22)(q34;q11), BCR/ABL1 fusion gene, multiple changes (≥3), monosomal karyotype), the intermediate risk group without significant prognostic markers and the group with favorable prognostic factors (t(8;21)(q22;q22), t(15;17)(q22;q21), t(16;16)(p13;q22)/inv(16)(p13q22), AML1/ETO, PML/RARa, CBFβ/MYH11 fusion genes). In remission cytogenetic investigations showed a normal karyotype without cytogenetically visible changes in all patients. Cytogenetic investigations at relapse were performed in 5 of 140 AML cases. Additional/secondary chromosomal aberrations in leukemic cells or new cells clones with multiple structural and numerical changes at relapse was not detected. Summary/Conclusion: Cytogenetic investigations had an important significance for diagnosis, prognosis and selection the optimal treatment strategy of AML. Besides the analysis of chromosome banding patterns it is necessary for patients with AML to apply molecular genetic studies, namely FISH and polymerase chain reaction (PCR). Taking into consideration the identified cytogenetic abnormalities AML patients were classified by risk groups. Presence of the additional/secondary chromosomal aberrations in leukemic cells or new cells clones with multiple structural and numerical changes at AML relapse is the one sign of clonal evolution and progression of disease.

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