Contributions
Abstract: PB1358
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
Using conventional cytogenetics, an abnormal karyotype can be detected in 60-85% of adult acute lymphoblastic leukemia (ALL) patients. Taking into consideration the identified cytogenetic abnormalities ALL 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 ALL.
Aims
Aim of this study was to detect the diagnostic and prognostic significance of chromosomal abnormalities in leukemic cells at different phases of ALL and to determine the frequencies of clonal evolution at ALL relapse.
Methods
Cytogenetic investigations of bone marrow and/or peripheral blood cells from 54 adult patients were performed during clinical evolution of ALL: 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 50 adult ALL patients were performed in newly diagnosed patients, in remission and at relapse. Structural (t(9;22)(q34;q11), 11q23 rearrangements, t(12;21)(p13;q22), del(17p), del(7q) and others) and numerical (monosomies, trisomies, tetrasomies, hyperdiploidy, hypodiploidy) chromosomal abnormalities in leukemic cells were found. Some genetic abnormalities (BCR/ABL and AF4/MLL fusion genes) were detected by molecular genetic methods (FISH). Spectrum of cytogenetic abnormalities had an important diagnostic and prognostic significance. Diagnosis of ALL was possible due to the presence of specific genetic markers that can confirm some types of ALL (ALL with t(9;22)(q34;q11), BCR/ABL gene, t(4;11)(q21;q23), hyperdiploidy, hypodiploidy). Taking into consideration the identified cytogenetic abnormalities ALL patients were classified by risk groups: the group of patients with adverse cytogenetic markers (hypodiploidy, t(4;11)(q21;q23), t(9;22)(q34;q11), multiple changes (≥3)), the intermediate risk group without significant prognostic markers and the group with favorable prognostic factors (t(12;21)(p13;q22), high hyperdiploidy). In remission cytogenetic investigations showed a normal karyotype without cytogenetically visible changes in all patients. Cytogenetic investigations at relapse were performed in 9 of 50 ALL cases. Presence of the additional/secondary chromosomal aberrations in leukemic cells or new cells clones with multiple structural and numerical changes at relapse was detected in 5 (56%) patients. This is the one sign of clonal evolution and progression of the disease.
Conclusion
Cytogenetic investigations had an important significance for diagnosis, prognosis and selection the optimal treatment strategy of ALL. Besides the analysis of chromosome banding patterns it is necessary for patients with ALL to apply molecular genetic studies, namely FISH and polymerase chain reaction (PCR). Taking into consideration the identified cytogenetic abnormalities ALL 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 ALL relapse is the one sign of clonal evolution and progression of disease.
Keyword(s): Acute lymphoblastic leukemia, Cytogenetic abnormalities
Abstract: PB1358
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
Using conventional cytogenetics, an abnormal karyotype can be detected in 60-85% of adult acute lymphoblastic leukemia (ALL) patients. Taking into consideration the identified cytogenetic abnormalities ALL 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 ALL.
Aims
Aim of this study was to detect the diagnostic and prognostic significance of chromosomal abnormalities in leukemic cells at different phases of ALL and to determine the frequencies of clonal evolution at ALL relapse.
Methods
Cytogenetic investigations of bone marrow and/or peripheral blood cells from 54 adult patients were performed during clinical evolution of ALL: 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 50 adult ALL patients were performed in newly diagnosed patients, in remission and at relapse. Structural (t(9;22)(q34;q11), 11q23 rearrangements, t(12;21)(p13;q22), del(17p), del(7q) and others) and numerical (monosomies, trisomies, tetrasomies, hyperdiploidy, hypodiploidy) chromosomal abnormalities in leukemic cells were found. Some genetic abnormalities (BCR/ABL and AF4/MLL fusion genes) were detected by molecular genetic methods (FISH). Spectrum of cytogenetic abnormalities had an important diagnostic and prognostic significance. Diagnosis of ALL was possible due to the presence of specific genetic markers that can confirm some types of ALL (ALL with t(9;22)(q34;q11), BCR/ABL gene, t(4;11)(q21;q23), hyperdiploidy, hypodiploidy). Taking into consideration the identified cytogenetic abnormalities ALL patients were classified by risk groups: the group of patients with adverse cytogenetic markers (hypodiploidy, t(4;11)(q21;q23), t(9;22)(q34;q11), multiple changes (≥3)), the intermediate risk group without significant prognostic markers and the group with favorable prognostic factors (t(12;21)(p13;q22), high hyperdiploidy). In remission cytogenetic investigations showed a normal karyotype without cytogenetically visible changes in all patients. Cytogenetic investigations at relapse were performed in 9 of 50 ALL cases. Presence of the additional/secondary chromosomal aberrations in leukemic cells or new cells clones with multiple structural and numerical changes at relapse was detected in 5 (56%) patients. This is the one sign of clonal evolution and progression of the disease.
Conclusion
Cytogenetic investigations had an important significance for diagnosis, prognosis and selection the optimal treatment strategy of ALL. Besides the analysis of chromosome banding patterns it is necessary for patients with ALL to apply molecular genetic studies, namely FISH and polymerase chain reaction (PCR). Taking into consideration the identified cytogenetic abnormalities ALL 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 ALL relapse is the one sign of clonal evolution and progression of disease.
Keyword(s): Acute lymphoblastic leukemia, Cytogenetic abnormalities