Background: The prognosis of chronic lymphocytic leukemia (CLL) has been improved dramatically, but there are limited studies focusing on CLL disease burden on a global scale. We aimed to evaluate the accurate assessment of the disease burden of CLL that may provide more detailed epidemiological information for rational policies. Methods: The main source of the data was the Global Burden of Disease (GBD) study 2019. Incident cases, death cases, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs) from 1990 to 2019 were used to describe the burden of CLL. Data about attributable risk factors were also extracted and analyzed. Bayesian age-period-cohort (BAPC) models were used to assess and project the incidence and mortality rates till 2030. Results: Globally, the incidence of CLL had been increasing. Deaths and DALYs decreased slightly. The burden of death and DALY is affected by socio-demographic index (SDI). The incidence rate, death rate, and DALY rate of CLL increased significantly with age. Male-to-female ratios of incidence rates varied in different SDI quintiles. Smoking, high body mass index, and occupational exposure to benzene or formaldehyde were the potential risk factors related to CLL. Global ASIRs might tend to increase until 2030, while ASDR would decrease until 2030. Conclusion: The disease burden of CLL decreased in higher SDI countries but increased in lower ones. Strategies for early detection of asymptomatic CLL, development of novel drugs, and measures against attributable factors should be implemented to combat CLL burden.

Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP. Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs. The circulating M2-like macrophage population defined as CD68+CD163+ and circulating MDSC population as CD11b+CD33+HLA-DR− were determined by flow cytometry. Plasma inflammatory cytokines were measured by multiplex ELISA. The percentages of MDSCs were found to be expanded in newly diagnosed patients of ITP, especially among those of the complete response (CR) group (p < 0.0001). Positive linear correlation was verified between percentages of M2-like macrophages and MDSCs. The same correlation was also determined in the CR group. After treatment, the percentages of M2-like macrophages and MDSCs were both increased significantly in CR group, while those patients among the PR + NR group manifested a significant numeric decrease of MDSCs but only a moderate decrease in M2-like macrophages. MIP-1α/CCL3 was negatively correlated with M2-like macrophages while MCP-1 possessed a positive correlation with M2-like macrophages, eotaxin-1/CCL11 was negatively correlated with MDSCs and interleukin-1β (IL-1β) was found to be negatively correlated with both M2-like macrophages and MDSCs. The present findings indicated critical roles of both circulating M2-like macrophages and MDSCs in ITP. The positive correlation between them might be related to inflammatory factors-mediated bidirectional interactions or partially due to their similar background patterns during differentiation. MIP-1α/CCL3, MCP-1, eotaxin-1/CCL11 and IL-1β might play a critical role in the expansion of both M2 macrophages and MDSCs population in ITP patients, which deserves further investigation.

Background: The first‐line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long‐term responses remains challenging. Low‐dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP.Methods: The M2 monocytes were identified by flow cytometry from peripheral blood mononuclear cells in healthy controls (HCs) and ITP patients. The expression of PPARγ, Arg‐1, DNMT3b and NLRP3, together with IL‐10 plasma levels was measured to examine its function. Bisulfite‐sequencing PCR was used to evaluate the methylation status of PPARγ promoter, and the binding affinity of KLF4 was measured by Cut&Tag. A sh‐PPARγ THP‐1 cell line was created to verify if low‐dose DAC‐modulated M2 macrophage polarization was PPARγ‐dependent. The passive ITP models were used to investigate the therapeutic effects of low‐dose DAC and its role in modulating polarization and immunomodulatory function of macrophages. NLRP3 inflammasome and reactive oxygen species were also tested to understand the downstream of PPARγ.Results: The M2 monocytes with impaired immunoregulation were observed in ITP. After high‐dose dexamethasone (HD‐DXM) treatment, M2 monocytes increased significantly with the elevated expression of PPARγ, Arg‐1 and IL‐10 in CR patients. Low‐dose DAC promoted M2 macrophage polarization in a PPARγ‐dependent way via demethylating the promoter of PPARγ, especially the KLF4 binding sites. Low‐dose DAC alleviated ITP mice by restoring the M1/M2 balance and fine‐tuning immunomodulatory function of macrophages. The downstream of the PPARγ modulation of M2 macrophage polarization might physiologically antagonize NLRP3 inflammasome.Conclusions: Low‐dose DAC promoted M2 macrophage polarization due to the demethylation within the promoter of PPARγ, thus enhanced the KLF4 binding affinity in ITP.