Monocyte subsets and their phenotypes during treatment with BCR‐ABL1 tyrosine kinase inhibitors for Philadelphia chromosome‐positive leukemia

Abstract

BCR-ABL1 tyrosine kinase inhibitors (TKIs) are effective agents in the treatment of Philadelphia chromosome-positive leukemia. However, vascular events have developed in some patients receiving each TKI. The perturbation of circulating monocyte subsets and their expressions of chemokine and scavenger receptors are associated with the development of cardiovascular events. Here, we examined the subsets of circulating monocytes and their phenotypes in 51 patients treated with imatinib, nilotinib, and dasatinib, and 11 healthy subjects in our institute. Except for a negative association between the number of classical monocytes and imatinib treatment, the proportions and numbers of monocyte subsets were not significantly associated with TKI treatment. However, chemokine receptors, CCR2, CX3CR1 on classical monocytes, and scavenger receptor, CD204, on intermediate and non-classical monocytes were significantly associated with TKIs. These data demonstrated the relationships between alterations of chemokine and scavenger receptors on different monocyte subsets and the TKI treatments.

Pattern of human monocyte subpopulations in health and disease

“…Among patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia treated with imatinib, the levels of classical monocytes were lower than those in the healthy control group. Additionally, no particular differences were found in the proportions of monocyte subsets between groups treated with imatinib, nilotinib or dasatinib and the control group 101 . In contrast to healthy blood donors, patients with ALL had remarkably lower levels of CD14+ monocytes following chemotherapy.…”

“…Additionally, no particular differences were found in the proportions of monocyte subsets between groups treated with imatinib, nilotinib or dasatinib and the control group. 101 In contrast to healthy blood donors, patients with ALL had remarkably lower levels of CD14+ monocytes following chemotherapy. Moreover, in the patients who were G-CSF treated, significantly more often intermediate monocytes and less often classical monocytes were observed.…”

Impact of Intestinal Microbiota on Reconstitution of Circulating Monocyte, Dendritic Cell, and Natural Killer Cell Subsets in Adults Undergoing Single-Unit Cord Blood Transplantation

“…Cells were stained with the following antibodies: PerCP-Cy5.5-conjugated anti-human CD3 (clone UCHT-1; Tonbo Biosciences, San Diego, CA), BV421-conjugated anti-human CD11c (clone 3.9; BioLegend, San Diego, CA), FITC-conjugated anti-human CD14 (clone M5E2; BioLegend), BV510-conjugated anti-human CD16 (clone 3G8; BioLegend), PerCP-Cy5.5-conjugated anti-human CD19 (clone HIB19; Tonbo Biosciences), PerCP-Cy5.5-conjugated anti-human CD20 (clone 2H7; Tonbo Biosciences), APC-Cy7-conjugated anti-human CD56 (clone HCD56; BioLegend), and PE-conjugated anti-human HLA-DR (clone L243; BioLegend). The gating strategy for classical, intermediate, and nonclassical monocytes, myeloid DCs (MDCs), plasmacytoid DCs (PDCs), and CD56 bright and CD56 dim NK cell subsets has been described previously [18][19][20][21]. Flow cytometry was performed using a FACSAria II (BD Bioscience, San Jose, CA), and data were analyzed using FlowJo 10.3 software (FlowJo, Ashland, OR).…”

Circulating unconventional T‐cell subsets during treatment with BCR‐ABL1 tyrosine kinase inhibitors for Philadelphia chromosome‐positive leukemia

“…PB samples were prepared as previously described. 6 The gating strategy for unconventional T cells is described in a previous report 7 ( Figure 1A). Compared with the control group, the number of white blood cells was significantly lower in the group that received imatinib (P = .009) and IFN (P = .009; Figure 1B).…”