Abnormal mitochondrial DNA in acute leukaemia and lymphoma

Electron microscopic examination was carried out on mitochondrial DNA molecules isolated from leucocytes in seven cases of acute leukaemia or leukaemic-phase poorly-differentiated lymphocytic lymphoma. There was a marked shift from the predominant circular monomeric form in normal leucocytes to circles with twice the normal circumference, as well as multiple interlocking circles in two of the four cases of untreated acute leukaemia, and in one of untreated lymphoma. This abnormal pattern of mitochondrial DNA evidently reflects an intrinsic aberration in the processing of mitochondrial DNA in some leukaemias and lymphomas, as it occurred in the absence of prior therapy with alkylating agents known to interact with DNA. Up to 47% of total mitochondrial DNA was present in such complex forms, which on steric grounds should be unsuitable as a template for replication of free monomers and possibly for messenger RNA production. The latter may be pertinent to previously reported abnormalities in acute leukaemia leucocytes which could be related to abnormal production of gene products of mitochondrial DNA.