CD79a promotes CNS-infiltration and leukemia engraftment in pediatric B-cell precursor acute lymphoblastic leukemia

摘要

a–c CD79a mRNA levels and further genes (all normalized to mRNA levels in the 697 cell line) were measured in diagnostic BM samples in a selected cohort of 100 pediatric BCP-ALL patients of mixed cytogenetics which contained 28 CNS-positive patients matched to 72 CNS-negative patients of corresponding sex and age5. a, b Bivariate correlation analysis between CD79a expression and a ZAP70 and b Interleukin-7-receptor (IL7R) were performed, Spearman correlation (two-tailed, respective 95% confidence interval (CI) [0.08789, 0.4605] and [0.2174, 0.5616]). c Univariate and multivariate logistic regression analysis for risk of initial CNS-involvement, controlled for age and white blood cell (WBC) count at diagnosis as well as TEL-AML and BCR-ABL positivity. *Based on expression as measured by RT-PCR of patient material at initial diagnosis. †Multivariate OR controlled for age and WBC count at diagnosis as well as TEL-AML and BCR-ABL positivity. §Reference category. Definitions of patient CNS status in Supplementary Material d Kaplan–Meier survival curve showing reduced isolated CNS-relapse-free survival in children with upregulated CD79a gene expression in diagnostic BM/peripheral blood (upregulation is defined as z-score for gene expression ≥1.2 which is equivalent to the 11.5% top CD79a-expressing patients; TARGET phase 1 dataset). e E2A-PBX1 + BCP-ALL blasts from seven different patient-derived xenograft (PDX) samples were injected into NSG mice ALL cells were recovered from spleen (SP) and CNS and subjected to quantitative real-time PCR (qPCR). QPCR shows the upregulation of CD79a at the transcription level in PDX cells recovered from the CNS relative to cells isolated from Sp, Mann–Whitney-U test, two-tailed, graphs show mean with standard error of n = 7 independent samples. f An upregulation of CD79a was also observed in CNS-BCP-ALL cells compared to SP-BCP-ALL cells in NSG-mice injected with bone marrow cells from BCP-ALL patients of different cytogenetic backgrounds (n = 5 independent patient samples) or CNS-tropic REH cells (TEL-AML1) as determined via qPCR. Relative quantification of CD79a mRNA levels normalized to 697 cells are shown for individual patients, P Patient, AU Arbitrary units. *P < 0.05, **P ≤ 0.01, ***P ≤ 0.001.