Figure 1.

Targeting mucosa-associated lymphoid tissue lymphoma translocation protein 1 efficiently kills B-cell acute lymphoblastic leukemia cells. (A) Peripheral blood mononuclear cells (PBMC) from patients with B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), or from healthy individuals were subjected to treatment with increasing doses of MI-2 for 48 hours (h). Cell viability was quantified using an MTS assay and is shown as percentage of the untreated control. (B) CD19-selected primary B-ALL cells collected from 3 patients were treated with the highly selective mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor Z-VRPR-fmk at 50 mM for 96 h. Cell viability was quantified using an MTS assay and is shown as a percentage of untreated control. (C) Waterfall plot showing percent changes in cell viability from baseline, quantified using an MTS assay, following a 9-day (9d) treatment with 50 mM Z-VRPR-fmk. Cells were split every three days. A total of 23 ALL cell lines tested representing the disease spectrum. Positive (TMD8) and negative (K562 and JVM2) controls are shown. (D) Correlation between percent change in cell viability following treatment with Z-VRPR-fmk as shown in (C), and the half maximal inhibitory concentration (IC₅₀) for MI-2 of B-ALL cell lines. T-PLL: T-cell prolymphocytic leukemia. *P<0.05. Error bars represent Standard Error of Mean. Columns with a brick pattern identify Philadelphia chromosome-positive cell lines.