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The Role of Cytogenetic Rearrangements in the Formation of Resistance in Relapse of Acute Lymphoblastic Leukemia

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Abstract

Cytogenetic rearrangements were studied in bone marrow cells of 24 patients with relapse of acute lymphoblastic leukemia (ALL). The authors have noted a high percentage of mosaic karyotypes (75.0%) with a predominance of abnormal clones combined with normal karyotypes (33.3%). Trisomies of chromosomes led to the formation of hyperdiploid clones, among which trisomies of chromosomes 6, 21, 15, and 5 were the most frequent events. Additional marker chromosomes were recorded in 22.2%. To characterize the mechanisms underlying the abnormal clone formation in relapse of ALL, structural chromosomal anomalies were recorded and divided into balanced (translocations, inversions) and imbalanced (deletions, isochromosomes, additional material of unknown origin, duplications, and imbalanced translocations) abnormalities. Losses of genetic material (deletions) (24.1%) and translocations (33.3%) were most frequently detected. The total number of events with translocation t(9;22)(q34;q11.2) reached 20.4%. The evolution of clonal chromosomal abnormalities occurred due to the emergence of additional numerical and imbalanced structural abnormalities. The comparison between chromosome abnormalities at diagnosis and in relapse of B-cell ALL has not led to any general mechanisms for the formation of chemotherapy-resistant clones. Trisomy of chromosome 5, deletion del(6)(q23), and translocation t(9;22) (q34;q11.2) were involved in the formation of chemotherapy-insensitive clones. The group of unfavorable prognosis included 95.8% of karyotypes.

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Funding

The study was conducted within the framework of the Scientific State Study Determination of Regularities in the Expression of Cellular-Molecular Markers by Lymphocytes and Tumor Cells for Assessing Disorders in Antitumor Immunity in Patients with Acute Myeloid Leukemia. The term of the study is from 2022 to 2024.

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Authors and Affiliations

  1. Institute of Hematology and Transfusiology, National Academy of Medical Sciences of Ukraine (NAMS of Ukraine), 1204060, Kyiv, Ukraine

    S. V. Andreieva

  2. Institute of Medical Molecular Diagnostics Laboratory (LLC IMMD), Pushya Vodytsia, Kyiv, Ukraine

    S. V. Andreieva, K. V. Korets & I. M. Skorokhod

  3. Institute of Blood Pathology and Transfusion Medicine, National Academy of Medical Sciences of Ukraine (NAMS of Ukaraine), 79000, Lviv, Lviv oblast, Ukraine

    O. M. Tsyapka

  4. Kyiv Municipal Clinical Hospital no. 9, 04112, Kyiv, Ukraine

    I. M. Serbin

Authors
  1. S. V. Andreieva
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  2. K. V. Korets
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  3. I. M. Skorokhod
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  4. O. M. Tsyapka
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  5. I. M. Serbin
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Corresponding authors

Correspondence to S. V. Andreieva, K. V. Korets, I. M. Skorokhod, O. M. Tsyapka or I. M. Serbin.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The correspondence of the studies to the principles of biomedical ethics was approved by the Ethics Committee of the State Enterprise Institute of Hematology and Transfusiology of the National Academy of Medical Sciences of Ukraine (Kyiv, Ukraine; Protocol No. 2 dated May 21, 2021).

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The authors of this work declare that they have no conflicts of interest.

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Andreieva, S.V., Korets, K.V., Skorokhod, I.M. et al. The Role of Cytogenetic Rearrangements in the Formation of Resistance in Relapse of Acute Lymphoblastic Leukemia. Cytol. Genet. 58, 39–45 (2024). https://doi.org/10.3103/S0095452724010067

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  • DOI: https://doi.org/10.3103/S0095452724010067

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