PMC9366004_01
(A) Increased immature/transitional B in the peripheral blood (upper panel; in red are represented CD10+CD21-CD27- transitional or immature B cells, in green CD10-CD21-CD27+ terminally differentiated B cells) and bone marrow (lower panel; in green CD34+CD38+CD10+). (B) Peripheral blood smears showing JMML in P1 (left panel): leukocytosis with monocytosis (triangle) and myeloid precursors (arrows). In the right panel, anisocytosis of platelets without leukocytosis or monocytosis in P2's peripheral blood smear. (C) CytoScan HD Array (SNP) analysis: allelic peak (AP) graph showing large copy neutral (CN = 2) loss of heterozygosity (LOH) regions in long arm of chromosome 11, in both patients; common LOH region includes CBL gene at band 11q23.3 (red line). (D) DNA methylation patterns in the reported patients showing low-methylation status. (E) STAT5 phosphorylation consistent with JMML in P1. AP, allele peaks; CHR, chromosome; CN, copy number state; HC, healthy control; IM, intermediate methylation; HM, high methylation; LM, low methylation; LOH, loss of heterozygosity; MRK, markers/markers number; P1 and P2, patients, START/END, cytoband start/end.
fped-10-935951-g001.jpg
PMC9366004_02_fped-10-935951-g001.jpg
F1
The CBC was normal but the PB smear analysis revealed platelet anisocytosis with giant forms and partially hypergranulated granulocytes were detected (Figure 1C). The single nucleotide polymorphism (SNP) array performed on PBMC suggested that CBL mutations were related to the loss of heterozygosity of chromosome 11q that included the CBL gene (Figure 1D). The DNA methylation profile was predicted to fit the low methylation class (Figure 1B). P1 showed p-STAT5 hyper-responsiveness to low doses (0.1 ng/ml) of GM-CSF assayed in CD33+CD34+ cells (Figure 1E). Here we have further characterized the B-cell phenotype showing that a consistent number of increased immature/transitional B cells still show the presence of the CD34 antigen (Figure 1B), thus pointing toward an abnormal proliferation of B-cell early precursors rather than increased B-cell output from the BM.
PMC9366004_02
(A) Increased immature/transitional B in the peripheral blood (upper panel; in red are represented CD10+CD21-CD27- transitional or immature B cells, in green CD10-CD21-CD27+ terminally differentiated B cells) and bone marrow (lower panel; in green CD34+CD38+CD10+). (B) Peripheral blood smears showing JMML in P1 (left panel): leukocytosis with monocytosis (triangle) and myeloid precursors (arrows). In the right panel, anisocytosis of platelets without leukocytosis or monocytosis in P2's peripheral blood smear. (C) CytoScan HD Array (SNP) analysis: allelic peak (AP) graph showing large copy neutral (CN = 2) loss of heterozygosity (LOH) regions in long arm of chromosome 11, in both patients; common LOH region includes CBL gene at band 11q23.3 (red line). (D) DNA methylation patterns in the reported patients showing low-methylation status. (E) STAT5 phosphorylation consistent with JMML in P1. AP, allele peaks; CHR, chromosome; CN, copy number state; HC, healthy control; IM, intermediate methylation; HM, high methylation; LM, low methylation; LOH, loss of heterozygosity; MRK, markers/markers number; P1 and P2, patients, START/END, cytoband start/end.
fped-10-935951-g001.jpg
PMC9366004_02_fped-10-935951-g001.jpg
F1
The CBC was normal but the PB smear analysis revealed platelet anisocytosis with giant forms and partially hypergranulated granulocytes were detected (Figure 1C). The single nucleotide polymorphism (SNP) array performed on PBMC suggested that CBL mutations were related to the loss of heterozygosity of chromosome 11q that included the CBL gene (Figure 1D). The DNA methylation profile was predicted to fit the low methylation class (Figure 1B). P1 showed p-STAT5 hyper-responsiveness to low doses (0.1 ng/ml) of GM-CSF assayed in CD33+CD34+ cells (Figure 1E). Here we have further characterized the B-cell phenotype showing that a consistent number of increased immature/transitional B cells still show the presence of the CD34 antigen (Figure 1B), thus pointing toward an abnormal proliferation of B-cell early precursors rather than increased B-cell output from the BM.