Fig. 3: Accelerated lymphomagenesis depends on the loss of HDAC1 enzymatic activity. | Leukemia

Fig. 3: Accelerated lymphomagenesis depends on the loss of HDAC1 enzymatic activity.

From: HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy

Fig. 3

A Schematic representation of mouse models used to generate NPM::ALK mice lacking the endogenous Hdac1 gene but expressing a catalytically dead, mutated HDAC1 protein (dHDAC1) that is unable to deacetylate proteins (NPM::ALK dHdac1KI mice). Cd4 NPM::ALK mice were crossed with CRE+ mice with floxed exons 6 of Hdac1 to obtain NPM::ALK mice with Hdac1KO. These were further crossed with mice containing the dHdac1 gene inserted into Rosa26 locus together with a floxed stop cassette. B Kaplan–Meier survival analysis of NPM::ALK mice (n = 25, blue line), NPM::ALK dHdac1KI mice (n = 19, pink line), and NPM::ALK Hdac1KO mice (n = 25, red line) in biological replicates. The median survival of different genotypes was compared using the Log-Rank (Mantel–Cox) test with GraphPad Prism (version 8.4.3). Statistical significance is indicated by **** for p < 0.0001. C Comparison of thymic tumor mass (g) of different genotypes. The mean with standard deviation (SD) is plotted. D Immunoblot showing protein levels of pALK and pSTAT3 in end-stage thymic tumors isolated from NPM::ALK (n = 4), NPM::ALK Hdac1KO (n = 4) and NPM::ALK Hdac1KI (n = 4) mice. Beta-actin was used as a loading control. The numbers on the left indicate the molecular weight of analyzed proteins in kiloDalton (kDa). E Quantification of HDAC1 (left) and HDAC2 (right) protein levels in end-stage thymic tumors of different genotypes from immunoblots shown in Supplementary Fig. 3. The mean with standard deviation (SD) is plotted. HDAC1 and HDAC2 protein levels were normalized according to beta-actin used as a loading control. Groups were compared using one-way ANOVA corrected for multiple comparisons with GraphPad Prism version 8.4.3. Statistical significance is indicated by ** for p < 0.01 and *** for p < 0.001. F HDAC activity levels were measured in end-stage thymic tumors of different genotypes (n = 5 biological replicates and n = 2 technical replicates were used for each genotype). Counts per minute beta (CPMB) values corresponding to HDAC activity levels were converted to percentages (%) with average NPM-ALK tumor HDAC activity set at 100%. The mean with standard deviation (SD) is plotted. Groups were compared using one-way ANOVA corrected for multiple comparisons using GraphPad Prism version 8.4.3. Statistical significance is indicated by * for p < 0.05.

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