AL-04. Cytogenetic analysis of complex chromosome aberrations in the patients with acute myeloid leukemia using multicolour fluorescent in situ hybridization

Summary

Cytogenetic diagnostics using multicolor fluorescent in situ hybridization (M-FISH) allows avoiding limitations associated with standard karyotyping and detect latent translocations, non-balanced exchanges, marker chromosomes, true monosomies in complex karyotype (CK) with three and more rearrangements. Complex karyotype as a distinct pathogenetic group within acute myeloid leukemia cohort (AML) is not rare and predicts a dismal prognosis, especially in combination with monosomic karyotype. Our aim was study profile of chromosome aberrations in CK of AML patients at onset and in relapse of the disease, including the conditions after allogeneic HSCT.

Materials and methods

The study included 34 patients with AML, observed at the R. Gorbacheva Memorial Institute of Pediatric Oncology, Hematology and Transplantation from 2010 to 2021. The study group consisted of 19 (56%) males and 15 females (44%) at a median age of 43 years, ranging between 3 mo and 71 years, including 27 patients (79%) with primary AML, and 7 cases (21%), with secondary AML developed from MDS. In 12 patients (35%), complex karyotype (СК) was observed initially, whereas 15 patients exhibited CK in relapse following chemotherapy (44%), and in 7 patients (21%), CK was revealed in post-transplant relapse.

Results

In general cohort, CK involved all the chromosomes. Most often were found the anomalies of chromosome No.5 (n=17, 5%); No.8 (n=17, 5%); No.7 (n=16, 5%); No.3 (n=14, 4%); No.11 (n=14, 4%), and No. 17 (n=13, 4%). Losses of chromosomal material mainly involved chromosome No.5 (n=11, 32%), No.7 (n=11, 3%), No.11 (n=9, 3%), whereas additional gains were detected for chromosome 5 (n=5, 15%), and No.8 (n=5, 15%). Non-balanced alterations dominated over the balanced, and occurred in 83%. Balanced rearrangements were rare and represented 17%. The ratio of balanced-to-nonbalanced chromosome aberrations was higher in AML with posttransplant relapses compared to AML relapses after chemotherapy (respectively, 1:19 and 1:2, р=0.03). Mean number of aberrations per cell in post-transplant relapses of AML was significantly higher than in AML relapses after chemotherapy (16 vs 5; р=0.001). Following HSCT performed in relapse, additional gain of material was more common for chromosomes 11 and 17. In 17 of 43 observations (48%), derivates were found which consisted of 3 to 5 segments of chromosomes 5, 7, 13, 17, 21 and looked like “pseudomonosomies”. Only 60% of true monosomies were proven by means of M-FISH.

Conclusions

The study has shown a cytogenetic heterogeneity of complex chromosomal anomalies in AML patients, with dominance of nonbalanced chromosome anomalies, especially, in the patients with posttransplant relapses. A combination of standard karyotyping and M-FISH allows precise identification of chromosomal aberrations, thus being important for determination AML prognosis, and detection of target markers for diagnostics of minimal residual disease.

Keywords

Acute myeloid leukemia, cytogenetics, complex karyotype, M-FISH.