Altered neutrophil immunophenotypes in childhood B‑cell precursor acute lymphoblastic leukemia

Abstract

An increasing number of evidences suggest a genetic predisposition in acute lymphoblastic leukemia (ALL) that might favor the occurrence of the driver genetic alterations. Such genetic background might also translate into phenotypic alterations of residual hematopoietic cells. Whether such phenotypic alterations are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL remains to be investigated. Here we analyzed the immunophenotypic profile of BM and peripheral blood (PB) maturing/matured neutrophils from 118 children with BCP-ALL and their relationship with the features of the disease. Our results showed altered neutrophil phenotypes in most (77%) BCP-ALL cases. The most frequently altered marker was CD10 (53%), followed by CD33 (34%), CD13 (15%), CD15/CD65 (10%) and CD123 (7%). Of note, patients with altered neutrophil phenotypes had younger age (p = 0.03) and lower percentages of BM maturing neutrophils (p = 0.004) together with greater BM lymphocyte (p = 0.04), and mature B-cell (p = 0.03) counts. No significant association was found between an altered neutrophil phenotype and other disease features. These findings point out the potential existence of an altered residual hematopoiesis in most childhood BCP-ALL cases.

Keywords: B-cell precursor acute lymphoblastic leukemia; altered neutrophil immunophenotype; childhood; multiparameter flow cytometry; residual hematopoiesis.

Figure 1. Illustrating examples of normal (A–G) and childhood BCP-ALL (H–V) BM mature/maturing neutrophil phenotypes for CD10 (C, J and R), CD33 (D, L and S), CD13 (E, M and T), CD15 plus CD65 (F, N and U) and CD123 (G, O and V)

Mature neutrophils are depicted in green while neutrophil precursors are shown in blue. Blast cells and other BM cell compartmens are depicted as black and grey events, respectively.

Figure 2. Frequency of BCP-ALL cases showing altered patterns of expression for individual (A) or multiple (B) markers on maturing/mature neutrophils

Figure 3. Frequency of childhood BCP-ALL cases with immunophenotypically altered maturing/mature neutrophils

(A) The distribution of patients with immunophenotypically normal vs. altered neutrophils is represented by bars whose height represents the number of cases per age group. The relative distribution of patients with normal (dark gray bars) vs. at least one altered phenotypic marker (light gray bars) within each age group is shown in percentage numbers above the bar. In (B) bars indicate the relative distribution of cases (i.e. percentages) within each age group according the number of altered markers on neutrophils. The overall percentage of cases with an altered neutrophil immunophenotype is shown per age group, as numbers above the corresponding bar.