Abstract
Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.
Highlights
According to the National Cancer Institute/Rome criteria 39,41, patients were classified into standard- and high-risk groups, where the former were those aged one to nine years with an initial total leukocyte count (TLC) of less than 50 × 1 09/L; had a DNA index of 1.16 or more; without Central nervous system (CNS)-3 status, testicular leukemia, t(9;22), t(4;11), t(1;19) associated with a pre-B immunophenotype, an MLL gene rearrangement, or near-haploidy; and bone marrow should not contain 5% or more leukemic blasts on day 15 of remission induction, while the remaining were considered high-risk patients, including those with leukemia with CNS involvement confirmed at diagnosis
This study included 31 children with B-cell acute lymphoblastic leukemia (B-Acute lymphoblastic leukemia (ALL)) with a mean age of 7 ± 0.7 years, who were further divided into three age groups for investigation
Accumulating evidence suggests that Tregs and Myeloid-derived suppressor cells (MDSCs) are associated with immune suppression in many tumors, it has not been proven whether a possible relationship exists between MDSCs and Tregs during tumor progression[6]
Summary
According to the National Cancer Institute/Rome criteria 39,41, patients were classified into standard- and high-risk groups, where the former were those aged one to nine years with an initial total leukocyte count (TLC) of less than 50 × 1 09/L; had a DNA index of 1.16 or more; without CNS-3 status, testicular leukemia (documented by ultrasonographic examination), t(9;22), t(4;11), t(1;19) associated with a pre-B immunophenotype, an MLL gene rearrangement, or near-haploidy; and bone marrow should not contain 5% or more leukemic blasts on day 15 of remission induction, while the remaining were considered high-risk patients, including those with leukemia with CNS involvement confirmed at diagnosis. A p-value of less than 0.05 was considered to be statistically significant
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