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I. V. Abramenko, N. I. Bilous, A. V. Movchan, A. A. Chumak, I. S. Dyagil, Z. V. Martina
State Institution «National Research Center for Radiation Medicine, Hematology and Oncology of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka St., Kyiv, Ukraine, 04050
THE IGLV3-21 LIGHT CHAIN ANALYSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Objective: to analyze the frequency of IGLV3A21 light chain expression in chronic lymphocytic leukemia (CLL) patients and correlate it with clinical outcome taking into account anamnestic exposure to the ionizing radiation (IR).
Methods. The study was performed in a group of 244 unselected CLL patients. The main group (n = 106) included
84 clean-up workers of the Chornobyl NPP accident, 16 inhabitants of radionuclide contaminated areas and 6 evacuees. The group of comparison consisted of 138 IR non-exposed patients. The diagnosis of CLL was based on clinical history, lymphocyte morphology, and immunophenotypic criteria. The immunoglobulin light chain (IGLV)
rearrangements were analyzed by Sanger sequencing using BIOMED-2 protocol in 132 patients, and in 112 patients
the IGLV3A21 chain presence was tested with real-time PCR method. The immunoglobulin heavy chain variable (IGHV)
gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data were
analyzed with the SPSS software package, version 20.0.
Results. Twenty four (9.8 %) IGLV3A21-positive cases were identified. Its frequency did not differ in the main group
(6.5 %) and in the group of comparison (12.5 %), p = 0.087. In the main group, IGLV3A21 gene expression was determined exclusively among clean-up workers. IGLV3A21-positive patients and patients with expression of other IGLV
genes were comparable by gender, age, stage at diagnosis, but IGLV3A21+ cases more frequently had mutated (M) IGHV
genes (66.7 % vs 29.5 %; p = 0.0001) and co-expressed IGHV3A21 gene (37.5 % vs 3.2 %; p = 0.0001). A significant
predominance of SF3B1 gene mutations among IGHV3A21-positive cases (47.4 % vs 21.2 %; p = 0.017) was revealed,
while the frequency of TP53 (p = 0.596) and NOTCH1 (p = 0.286) gene mutations did not differ depending on the
expression of IGLV genes. Among patients with M IGHV genes periods of progression-free (87 mo. vs 156 mo. in
IGLV3A21- cases; p = 0.009) and overall survival (106 mo. vs 167 mo., respectively; p = 0.021) were shorter in
IGLV3A21-positive cases. It has been showed that Binet stage, age ≥ 65 years, and IGLV3A21 gene expression were powerful adverse prognostic factors for overall survival in CLL patients with M IGHV genes. Significant factors for predicting progression-free survival were: Binet stage, IGLV3A21 gene expression and initial leukocytosis ≥ 70 x 109/L. These
data were common to patients of both observed groups regardless of radiation anamnesis.
Conclusions. Our data confirmed unfavourable prognostic value of IGLV3A21 for prediction of progression-free survival and overall survival in CLL patients with M IGHV genes, regardless of radiation anamnesis.
Key words: chronic lymphocytic leukemia; IGHV genes; IGLV3A21 gene; Chornobyl NPP accident; progression-free survival; overall survival; SF3B1 mutations.
Problems of Radiation Medicine and Radiobiology.
2025;30:299-309. doi: 10.33145/2304-8336-2025-30-299-309
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