DNA methylation landscape of C/G+ pediatric acute myeloid leukemia (AML) and cell line models. (IMAGE)

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DNA methylation landscape of C/G+ pediatric acute myeloid leukemia (AML) and cell line models.

Caption

(A) Overview of the cohort, including all de novo acute megakaryoblastic leukemia subtypes (n = 75), compared with mononuclear cells derived from the bone marrow (BM) of non-cancer donors under 18 years of age (n = 10). This analysis also incorporated two CBFA2T3-GLIS2 (C/G)-positive AML cell lines (M07e and WSU-AML), three non-C/G AML cell lines (KASUMI-1, KG1A, and ME-1), as well as CD34+ hematopoietic stem cells (HSC) derived from umbilical cord blood, and CD41+ megakaryocytic progenitors (MK) differentiated from CD34+ HSCs.

 

(B) The Venn diagram illustrating differentially methylated CpGs (DMCs) shared between C/G+ pediatric AML cases, representing both megakaryoblastic (M7) and non-M7 lineages, corresponding to 24,479 differentially methylated genes (DMGs).

(C) The Venn diagram showing the overlap of DMCs between C/G+ cell lines (M07e and WSU-AML) when compared with HSC and MK progenitors, identifying 33,561 DMGs.

(D) Intersection analysis of DMGs across C/G+ pediatric AML patients and cell lines, revealing 19,410 DMGs unique to the C/G fusion. (E, G) Frequency distribution of DMCs in C/G+ pediatric AML patients

 

(E) and C/G+ cell lines (G), categorized by their genomic locations across promoters, gene bodies, and intergenic regions. (H) The heatmap illustrating the clustering of major de novo acute megakaryoblastic leukemia patients and normal BM (NBM) isolates based on DNA methylation profiles at promoters and gene bodies of C/G-restricted genes. (I) The heatmap of DNA methylation at promoters and gene bodies of C/G-restricted genes, comparing C/G+ and non-C/G AML cell lines with HSCs and MK progenitors, demonstrating distinct clustering patterns.

Credit

Samrat Roy Choudhury, Akhilesh Kaushal, Pritam Biswas, Cory Padilla, Jay F. Sarthy, Arundhati Chavan, Giselle Almeida Gonzalez, Soheil Meshinchi, Jason E. Farrar

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