Fig. 2 | Leukemia

Fig. 2

From: GATA1 epigenetic deregulation contributes to the development of AML with NPM1 and FLT3-ITD cooperating mutations

Fig. 2

Decreased GATA1 expression levels in human and mouse NPM1/FLT3-ITD mutated acute myeloid leukemia (AML) depends on promoter methylation. a (i) Analysis of DNA methylation at the mouse GATA1 locus by sequencing of PCR clones derived from sodium bisulfite–treated mouse genomic DNA extracted from the bone marrow (BM). Each row of circles represents the sequence of an individual clone; open circles indicate unmethylated CpG sites and closed circles indicate methylated CpG sites. (ii) Methylation status of the GATA1 promoter as determined by the Methylight assay. (iii) GATA1 protein expression in the BM of Aza-treated mice (n = 5). (iv, v) Changes in white blood cell (WBC) and platelet (PLT) counts of Npm1+/TCTG;Flt3+/ITD mice treated with Aza (n = 5 to 10 per treatment group). (vi) Frequencies of MEP and Ter119 cells in the BM of Aza-treated mice (n = 5 to 12 per treatment group). (vii) Frequencies of Gr1+/cKit+ immature and Gr1+Mac1+ mature myeloid cells in the spleen of untreated vs 5-Aza-treated leukemic mice (n = 5). b (i) GATA1 mRNA average expression in AML patients with NPM1/FLT3-ITD mutation compared to unmutated, NPM1 and FLT3-ITD single mutant (p < 0.05 comparing all the groups); pie charts indicate the percentage of patients with GATA1 expression below the median in the indicated mutation group. (ii) GATA1 promoter methylation frequency in AML patients with NPM1/FLT3-ITD mutation (n = 8) as compared to unmutated (n = 4), NPM1 (n = 8) and FLT3-ITD (n = 4) single mutant. (iii) GATA1 mRNA levels in the BM of human AML patients (n = 3) before and after in vivo Aza treatment. N.S. not significant; *p < 0.05, **p < 0.01; ***p < 0.001; unpaired t-test with Welch’s correction

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