Is Superinstability Of Karyotype Of Acute Myeloid Leukemia “Relic Radiation From Big Bang” Of Chromosome Homeostasis On MDS Stage?

In some cases of the cytogenetic analysis patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) there are increase frequency non-clonal disorders (“cytogenetic noise”)  in combination with complex (≥ 3 chromosomal aberration) clonal disorders. It is not infrequently manifested in the form of superinstability of the karyotype. In this case every aberrant cell is genetic different from each other. It is obvious that super unstable karyotype has a poor prognosis even more than complex clonal disorders, since due to the high genetic instability is a strong possibility of mutations that cause resistance to chemotherapy. In other words, the high level of “cytogenetic noise” on background of complex clonal disorders can be used as a marker of highly aggressive course of AML and MDS. The aim of our study was to determine the effect of superinstability of the karyotype on the current and prognosis of AML and MDS.

Thus, 157 patients with cytogenetic survey from register of AML and MDS by Kirov Research Institute of Heamatology were included in our research. They are 73 men, 84 women have the age from 21 to 81 (Me 55) years. Among them 34 patients have MDS and 123 – AML excluding promyelocytic leukemia. Chromosomal aberration were determined from bone marrow aspirate by standard cytogenetic method (GTG-method). Was evaluated at least 20 metaphase cells.

Among MDS patients the prevalence of superinstability of the karyotype was 29%, while among AML – only 4%, χ2=16.9, p<0.0001. In MDS group 2 patients (20%) are RAEB-1, 7 (70%) – RAEB-2, 1 (10%) – unspecified MDS. In AML group 2 patients (40%) are M2 FAB, 1 (20%) – M4 FAB, 2 (40%) - unspecified AML. Given that this type of cytogenetic of high instability is a characteristic feature of MDS, we can suppose, that AML with such instability always have the preliminary MDS stage with cell superinstability of the karyotype. In other words, the superinstability of the karyotype in AML can be regarded as “relic radiation from Big Bang” of chromosome homeostasis, which occurred at the preliminary MDS stage. The median of overall survival among all these patients treated by standard chemotherapy was 3 month, maximum survival – 16 month. The median of overall survival in AML patients was 1 month, MDS – 3.5 months. All patients were died.

A chromosomal superinstability of tumor cells that greatly enhances the aggressiveness of the current AML and MDS, leading to chemotherapy resistance and dramatically reduces the overall survival patients. Superinstability of the karyotype determines the group of patients untreatable by standard chemotherapy. The allogeneic bone marrow transplantation need in these cases.

No relevant conflicts of interest to declare.