Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy

Abstract

The additional molecular and chromosomal abnormalities (ACA) in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML) progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation) were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase) were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months). 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005). The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR) is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17)(q10) are poor prognostic factors of TKI treatment failures.

About the authors

O. Yu. Vinogradova

Hematological Research Center, Ministry of Health of Russia

Author for correspondence.
Email: olgavinz@mail.ru
Russian Federation

E. A. Aseeva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

A. V. Vorontsova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

A. G. Turkina

Hematological Research Center, Ministry of Health of Russia

Russian Federation

A. L. Neverova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

O. V. Lazareva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

E. Yu. Chelysheva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

G. A. Gusarova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

T. I. Kolosheinova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

L. Yu. Kolosova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

S. R. Goryacheva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

M. V. Vakhrusheva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

S. M. Kulikov

Hematological Research Center, Ministry of Health of Russia

Russian Federation

I. A. Tishchenko

Hematological Research Center, Ministry of Health of Russia

Russian Federation

L. V. Dyachenko

Hematological Research Center, Ministry of Health of Russia

Russian Federation

A. I. Udovichenko

Hematological Research Center, Ministry of Health of Russia

Russian Federation

G. A. Alimova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

E. V. Kleina

Hematological Research Center, Ministry of Health of Russia

Russian Federation

L. A. Grebenyuk

Hematological Research Center, Ministry of Health of Russia

Russian Federation

M. L. Konnova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

S. Yu. Smirnova

Hematological Research Center, Ministry of Health of Russia

Russian Federation

N. D. Khoroshko

Hematological Research Center, Ministry of Health of Russia

Russian Federation

E. V. Domracheva

Hematological Research Center, Ministry of Health of Russia

Russian Federation

References

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