Complementary Diagnostic and Prognostic Value of Parallel Karyotyping and Molecular Diagnostics in Patients with Acute Leukemias.

Chromosomal aberrations analyzed by cytogenetic and molecular methods are major prognostic factors determining treatment options in patients with acute leukemias. The aim of this study was to compare cytogenetic and molecular methods as diagnostic and prognostic tools in patients with acute leukemias. Sixty one previously untreated patients with acute leukemias (AML - 43, ALL - 18) were studied for the presence of chromosomal translocations and corresponding fusion genes [AML1-ETO t(8;21), CBFB-MYH11 inv(16), PML-RARA t(15;17), BCR-ABL p190, p210 t(9;22), MLL-AF4 t(4;11), TEL-AML1 t(12;21), E2A-PBX1 t(1;19), SIL-TAL1 del(1)] using both molecular (RT-PCR, nested PCR) and cytogenetic (GTG) methods. Molecular diagnostics was performed from RNA isolated from bone marrow samples according to BIOMED-1 protocol. Cytogenetic studies were carried out with classical GTG and FISH methods. G-banded mitoses of bone marrow specimen were analysed according to ISCN. Chromosomal aberrations were found in 32.8% patients using GTG method while the parallel molecular tests revealed related fusion genes in 50.8% patients. In 8.5% patients cytogenetic analysis was not performed because of lack of metaphases in cultured cells. All cytogenetic aberrations found in GTG were also confirmed in RT-PCR. Stratification into cytogenetic risk groups was performed after applying combined analysis of karyotyping and molecular tests. Low cytogenetic risk group consisted of 32.8% patients including 11.5% diagnosed with GTG and additionally 21.3% patients after applying molecular tests. The intermediate and high cytogenetic risk group consisted of 32.8% and 34.4% respectively using combined cytogenetic and molecular diagnostics. In low cytogenetic risk group, 85% of patients achieved complete remission (CR), early deaths were found in 15% and none of the patients presented primary chemotherapy resistance. In intermediate risk group CR were obtained in 80%, chemoresistance in 10% and early deaths were observed in 10% of patients. In high cytogenetic risk group, CR were achieved in only 23.8% and chemoresistance occured in 76.2% of the patients. In conclusion we suggest that molecular and cytogenetic tests are complementary methods and should be used in parallel in the initial diagnosis of patients with acute leukemias. This seems to be critical for obtaining the accurate diagnosis, cytogenetic risk assessment and choosing an optimal treatment options.