Chronic myeloid leukemia: practical insights into epidemiological and biological patterns

Background. The diagnostic value of lactate dehydrogenase (LDH) levels and the presence of T315I and K222R/665A mutations in BCR-ABL1 transcripts remains under investigation, aiming to improve therapeutic strategies that address tyrosine kinase inhibitor (TKI) resistance, manage relapse, and enhance disease monitoring. Objectives. This study aimed to assess the epidemiological and biological patterns of chronic myeloid leukemia (CML) from a practical perspective. Material and methods. A cross-sectional and cohort descriptive study was conducted on 134 prospective and retrospective CML patients treated between 2015 and 2024 at the Institute of Oncology in Moldova. Quantitative RT-PCR and, in selected cases, next-generation sequencing were used to detect BCR-ABL1 p210 and p190 transcript expression. Venous blood samples were analyzed for alkaline phosphatase, LDH, and the presence of T315I and K222R/665A mutations to evaluate their biological relevance. Results. In the studied cohort of patients with CML, the diagnosis was confirmed in the early or late chronic phase in 122 (91.04 ± 2.32%) patients, and in the accelerated or acute phase in 12 (8.96 ± 2.03%) patients. In the majority of CML cases (78.5%), elevated lactate dehydrogenase levels were observed in venous blood. A statistically significant increase was recorded for both alkaline phosphatase (p < 0.05) and lactate dehydrogenase (p < 0.01), with values rising respectively from 207.50 U/L and 460.07 U/L in the early chronic phase to 282.68 U/L and 1059.70 U/L in the acute phase. In 69.8% of cases, the expression of BCR-ABL1 transcripts exceeded 65%. The b3a2 transcript was detected in 68 (56.7%) cases, while the b3a3 transcript was found in only 2 (1.7%) cases (p < 0.001). CML relapsed in 11 (55.0%) patients with elevated lactate dehydrogenase levels at diagnosis, and in 7 (63.6%) patients with T315I and K222R/665A mutations. The survival of patients without resistance mutations ranged from 62 to 287.3 months (M = 154.7 ± 3.62), while the survival of patients with resistance mutations varied from 45.7 to 283.4 months (M = 148.5 ± 4.31). Conclusions. BCR-ABL1 transcript expression correlates with disease progression and may offer higher diagnostic sensitivity than cytogenetic methods. Elevated LDH levels are relevant for phase determination and relapse risk assessment. Positive correlations were observed between LDH levels and BCR-ABL1 transcript expression.