Теоретические и практические аспекты изучения фракций BAALC-экспрессирующих гемопоэтических стволовых клеток у больных острыми миелоидными лейкозами с мутациями в гене FLT3

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AIM. To study the fractions of BAALC-expressing (BAALC-e) leukemic hematopoietic stem cells (LHSCs) in acute myeloid leukemia (AML) patients with isolated mutations in the FLT3 gene as well as their combinations with the mutations in the NPM1 gene. MATERIALS & METHODS. The study enrolled adult AML patients with the common element of having isolated FLT3 mutations in the genome (n = 25). The control group (n = 21) consisted of AML patients with mutations in both FLT3 and NPM1. The patients (n = 46) were aged 18–84 years (median 52 years), there were 26 women and 20 men. Non-random chromosomal aberrations, including those of a complex nature (≥ 3 lesions per metaphase), were identified in 13 patients with isolated FLT3 mutation and in 1 patient with both FLT3 and NPM1 mutations. Quantitative real-time PCR was used to measure the level of BAALC, WT1, and EVI1 expressions by the cells in bone marrow aspirate. Thresholds for distinguishing between high and low levels of BAALC and EVI1 expression were considered to be 31 % and 10 %, respectively, and the thresholds for WT1 and FLT3 allele ratio were 250 copies/104 ABL1 copies and 0.5, respectively. РЕЗУЛЬТАТЫ. An increased BAALC expression level roughly reflecting the fraction size of BAALC-e LHSCs was detected in 20/25 (80 %) patients with isolated FLT3 mutations. This was observed together with an increased level of WT1 (n = 22) and EVI1 (n = 7) expression. In all patients with both FLT3 and NPM1 mutations (control group, n = 21), the BAALC and EVI1 expression levels were below the threshold, which did not affect WT1 expression. This observation suggests to question the random nature of the identified decrease of BAALC and EVI1 expressions, which can be hypothetically accounted for by a low count of CD34-positive LHSCs in the bone marrow of AML patients with NPM1 mutations. Serial measurements of these molecular parameters under therapy for AML with FLT3 +/– NPM1 mutations show the feasibility of their use in assessing the therapy efficacy or the need for its correction, if required. CONCLUSION. The data presented in this paper clearly indicate that clinical trials need to intensively apply serial analysis of the fractions of BAALC-expressing leukemic HSCs in AML patients with FLT3 mutations. This approach allows for better molecular monitoring of the therapy efficacy for this challenging category of AML patients.