Subsets of AML display upregulated mtDNA biosynthesis and cytoplasmic nucleoside kinase expression. (A) Expression pattern and hierarchical clustering of microarray data from 542 primary human AML and 73 normal nonleukemic and healthy bone marrow samples¹²  for 8 mtDNA biosynthesis genes. The 4 main AML mtDNA biosynthesis clusters (purple, green, red, cyan) were designated as 1, 2, 3, and 4. A red color indicates a higher expression compared with the mean of all AML and normal samples; a blue color indicates a lower expression. (B) Boxplot of scaled data distribution (z-score) of the 4 AML clusters and normal samples for each of the 8 mtDNA biosynthesis genes from panel A. Values displayed on boxplot indicate median z-score values. Two-sided t tests were applied to estimate significance of differences between AML and normal clusters. (C-D) Boxplot of scaled data distribution (z-score) of cytoplasmic nucleoside kinases CMPK1 (C) and NME1-2 (D) between the 542 primary human AML and the 73 normal samples. Two-sided t test was applied to estimate significance of differences between these 2 groups. (E) Total proteins were extracted and immunoblotted for POLG, cytoplasmic nucleoside kinases CMPK1 and NME2, and loading control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 12 human primary AML cells (A1-A12) and 5 normal G-CSF–mobilized PBSCs.