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Novel non‐neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia
Author(s) -
Järviaho T.,
HurmeNiiranen A.,
Soini H.K.,
Niinimäki R.,
Möttönen M.,
Savolainen E.R.,
Hinttala R.,
HarilaSaari A.,
Uusimaa J.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13100
Subject(s) - mitochondrial dna , oxidative phosphorylation , mitochondrion , biology , genetics , missense mutation , mutation , gene , microbiology and biotechnology , biochemistry
Mitochondria produce adenosine triphosphate ( ATP ) for energy requirements via the mitochondrial oxidative phosphorylation ( OXPHOS ) system. One of the hallmarks of cancer is the energy shift toward glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Mitochondria have their own genome (mitochondrial DNA [ mtDNA ]) encoding for 13 essential subunits of the OXPHOS enzyme complexes. We studied mtDNA in childhood acute lymphoblastic leukemia ( ALL ) to detect potential pathogenic mutations in OXPHOS complexes. The whole mtDNA from blood and bone marrow samples at diagnosis and follow‐up from 36 ALL patients were analyzed. Novel or previously described pathogenic mtDNA mutations were identified in 8 out of 36 patients. Six out of these 8 patients had died from ALL . Five out of 36 patients had an identified poor prognosis genetic marker, and 4 of these patients had mtDNA mutations. Missense or nonsense mtDNA mutations were detected in the genes encoding subunits of OXPHOS complexes, as follows: MT‐ND1 , MT‐ND2 , MT‐ND4L and MT‐ND6 of complex I; MT‐CO3 of complex IV ; and MT‐ATP6 and MT‐ATP8 of complex V. We discovered mtDNA mutations in childhood ALL supporting the hypothesis that non‐neutral variants in mtDNA affecting the OXPHOS function may be related to leukemic clones.