Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with early switch to the monocytic lineage and loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced switch detectable by flow cytometry (FC). Using exome and RNA sequencing, switch was found to positively correlate with three different genetic subtypes: PAX5-P80R mutation (5 cases with switch out of 5), rearranged DUX4 (DUX4r; 30 cases of 41) and rearranged ZNF384 (ZNF384r; 4 cases of 10). Expression profiles or phenotypic patterns correlated with genotypes, but within each genotype they could not identify cases who subsequently switched. If switching was not taken into account, the B-cell-oriented FC assessment underestimated the minimal residual disease level. For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the B-cell phenotype. Discordance on day 33 was observed in all the DUX4r, PAX5-P80R and ZNF384r subtypes. Importantly, despite the substantial phenotypic changes, possibly even challenging the appropriateness of BCP-ALL therapy, the monocytic switch was not associated with a higher incidence of relapse and poorer prognosis in patients undergoing standard ALL treatment.

• MeSH
• PAX5 Transcription Factor genetics   MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * MeSH
• B-Lymphocytes MeSH
• Immunophenotyping MeSH
• Humans MeSH
• Mutation MeSH
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma * diagnosis   genetics   MeSH
• Neoplasm, Residual MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• PAX5 Transcription Factor MeSH
• PAX5 protein, human MeSH Browser

M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16-) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection.

• MeSH
• Allografts MeSH
• CD163 Antigen MeSH
• Antigens, Differentiation, Myelomonocytic blood   MeSH
• Biomarkers blood   MeSH
• Antigens, CD blood   MeSH
• Adult MeSH
• Interleukin-10 metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Macrophages immunology   metabolism   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Monocytes immunology   metabolism   MeSH
• Receptors, Cell Surface blood   MeSH
• Graft Rejection blood   etiology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Kidney Transplantation * MeSH
• Up-Regulation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• CD163 Antigen MeSH
• Antigens, Differentiation, Myelomonocytic MeSH
• Biomarkers MeSH
• Antigens, CD MeSH
• IL10 protein, human MeSH Browser
• Interleukin-10 MeSH
• Receptors, Cell Surface MeSH