The prognostic value of leukemic stem cells percentage in B-lineage childhood acute lymphoblastic leukemia

Tarasova A.V.1, Shman T.V.2, Movchan L.V.1

A.V. Tarasova, T.V. Shman, L.V. Movchan

Belarusian Research Сenter for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus

One generally accepted theory is that leukemia is maintained by leukemia stem cells (LSCs), which play the central role in drug resistance and metastasis. It would be of great interest to study the quantity of LSCs during follow-up and their prognostic impact on different types of leukemia. Moreover, developing LSCs-targeted therapy may provide, in combination with standard therapy, a way to eradicate the leukemic process. The aim of our study was to evaluate LSCs percentage and their prognostic meaning for childhood B-precursor acute lymphoblastic leukemia. Patients and Methods: We investigated cord blood samples from 87 children with B-ALL. The percentage of LSCs with phenotype CD34+CD38-CD19+ (Wilson K., 2010) in the blast population was determined at diagnosis. Minimal residual disease (MRD) was assessed by detection of aberrant immunophenotype using flow cytometry (FC 500, “Beckman-Coulter”). Comparisons of patient’s characteristics were performed using the Mann — Whitney U-test. Data were presented as median and percentiles (25–75) and accepted as reliable at < 0.05. Results: We observed that initial increased level of CD34+CD38-CD19+ cells correlates with a poor response to induction chemotherapy. The median content of CD34+CD38-CD19+ was 0.13% (0.01–3.7) for MRD-negative ( 0.01% of blasts) patients at 15th day of induction chemotherapy ( and 0.6% (0.06–3.7) respectively (< 0.05). Conclusion: Thus, increased LSCs percentage correlates significantly with a lack of complete response in patients with childhood B-ALL. CD34+CD38-CD19+ compartment at diagnosis was higher for MRD-positive patients at 15 and 36 days of chemotherapy. The prognostic impact of the MRD stem cell quantity might improve the already strong impact of total MRD quantity on outcome. Identification of new therapeutic targets based on LSCs biological features is the aim of the future studies.

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