Rearrangement of 11q23 Chromosome Region in Acute Myeloid Leukemias in Children

EV Fleishman1, OI Sokova1, AV Popa1, GA Tsaur2,3,4, LN Konstantinova1, OM Plekhanova2, MV Strigaleva2, ES Nokhrina2, VS Nemirovchenko1, OR Arakaev2,3

1 NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 District Children’s Hospital No. 1, 32 S. Deryabinoy str., Yekaterinburg, Russia, 620149

3 Research Institute of Medical Cell Technologies, 22a Karla Marksa str., Yekaterinburg, Russia, 620026

4 The First President of Russia BN Yeltsin Ural Federal University, 19 Mira str., Yekaterinburg, Russia, 620002

For correspondence: Elena Vol’fovna Fleishman, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)323-57-22; e-mail: flesok@yandex.ru

For citation: Fleishman EV, Sokova OI, Popa AV, et al. Rearrangement of 11q23 Chromosome Region in Acute Myeloid Leukemias in Children. Clinical oncohematology. 2016;9(4):446–55 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-446-455


ABSTRACT

Aim. To study characteristics of 11q23 involvement, age-specific differences in the incidence of these chromosomal markers in acute myeloid leukemias (AML) in children, and to determine their prognostic significance in patients treated according to the protocols applied in leading Russian pediatric hematological clinics.

Methods. The chromosomal analysis of bone marrow and peripheral blood cells has been performed prior to initiation of treatment in 395 children with primary AML aged from 0 to 16 years. The patients were treated in pediatric hematological clinics of Moscow and Moscow Region and in Yekaterinburg District Children’s Hospital No. 1. Clinical outcomes of 300 followed-up pediatric patients treated with similar modern therapy protocols were analyzed to evaluate the prognostic impact of 11q23/MLL abnormalities. To determine the incidence of 11q23/MLL rearrangements in AML of different age groups, we examined not only children, but also adult patients (= 212).

Results. In AML, the frequency of changes in the 11q23 region exceeded 40 % in children aged from 0 to 2 years. The frequency decrease with age and in patients over 40 years it was only 2 %. Significant heterogeneity of changes in karyotypes with 11q23/MLL rearrangements was observed: both various translocations with different regions of other chromosomes, and 11q23 deletions were detected. In addition, a great variability of numerical and structural additional chromosomal abnormalities was observed. The 10-year relapse-free survival rates (30.4 ± 6.7 %) and overall survival rates (35.1 ± 7.0 %) in AML with changes in the 11q23 region (= 61) were significantly lower than those in patients from the intermediate risk group (n = 103): 48.9 ± 5.8 % and 43.8 ± 7.5 %, respectively (= 0.035). The data are close to those in the high-risk group (n = 44): 35.9 ± 8.1 % and 38.3 ± 7.6 %, respectively. The study failed to confirm the published data that t(9;11) is a more favorable prognostic factor, and that t(6;11) and t(10;11) are less favorable ones than all other 11q23 translocations. Our results did not confirm a negative prognostic effect of additional chromosome abnormalities associated with 11q23 rearrangements.

Conclusion. Pediatric AML patients with 11q23 abnormalities should be included in a high-risk group if therapy is performed according protocols applied in leading hematological centers of Russia.


Keywords: pediatric acute myeloid leukemias, 11q23/MLL rearrangements, risk groups.

Received: May 12, 2016

Accepted: June 15, 2016

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