Leukemic mitochondria. II. Acute monoblastic leukemia.

Qualitative and quantitative ultrastructural studies were performed on mitochondria of leukemic monoblasts from 15 patients with acute monoblastic leukemia. Similar comparative observations were made on mitochondria of myeloblasts from 14 hematologically normal controls. No significant quantitative differences were noted between normal and leukemic mitochondria. Area measurements were approximately equal. Qualitative differences between the two groups consisted of increased numbers of irregularly shaped mitochondria, damaged mitochondrial membranes, mitochondria with damaged matrix, and small granules in mitochondria in the leukemic group. Leukemic cells exhibited nuclear-mitochondrial contact and virus-like particles within damaged mitochondria. To confirm the presence of virus-like particles and to aid in our understanding of nuclear-mitochondrial interaction, a C-type virus producer MSV-MLV infected rat embryo cell culture was used for additional analysis. Mitochondrial abnormalities and increased frequency of virus in damaged mitochondria, often attached to mitochondrial membranes, were noted. Several lysosomes exhibited accumulations of virus and budding into lysosomes from lysosomal membranes. Mitochondria are important organelles in glycolytic-oxidative phosphorylation pathways, and carry extranuclear genetic information. Further studies of morphologic and biochemical abnormalities of leukemic mitochondria and the interaction between the mitochondria and the nuclei in leukemic cells are needed to provide researchers with data on extranuclear factors operating in oncogenesis.

Leukemic mitochondria. III. Acute lymphoblastic leukemia.

Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic lymphoblasts in 6 patients with acute lymphoblastic leukemia. Similar studies were performed on lymphoblasts from lymph nodes obtained from 10 surgical patients without nodal diseases. Significant quantitative differences between normal and leukemic mitochondria were not observed except for a difference in mitochondrial area per cell (P less than 0.05). This was not significant lacking, qualitative diffecrences were observed. These abnormalities included rare giant mitochondria, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and nucleus during interphase. Fifty-three percent of the leukemic lymphoblasts contained polyribosomes, as compared to 25% of the normal lymphoblasts. The cells with the polyribosomes contained the giant mitochondria. The leukemic lymphoblasts had an appearance similar to transformed lymphocytes resulting from an immunologic stimulus. This suggests that acute lymphoblastic leukemia may be a disease which is associated with an immunologic response. From the available ultrastructural and biochemical data, it would seem that the leukemic lymphoblast is a product of an abnormal metabolism which affects its ability to differentiate. These ultrastructural findings seem to indicate the need for biochemical investigation of leukemic mitochondria. (Am J Pathol 78:49-58, 1975

Leukemic mitochondria. I. Acute myeloblastic leukemia.

Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic myeloblasts in 3 patients with myeloblastic leukemia and in 3 patients with myelomonoblastic leukemia. In addition, to confirm the presence of virus-like particles within mitochondria and better understand the interaction between the virus and mitochondrion, a rat embryo tissue culture infected with MSV-MLV (Moloney sarcoma virus-Moloney leukemia virus) was selected for detailed electron microscopic examination. Significant quantitative differences between normal and leukemic human mitochondria were not observed. However, qualitative abnormalities were found in the human leukemic mitochondria and in the tissue culture material. These abnormalities included variable forms of the leukemic mitochondria (twisted, tear-drop and irregular shapes), fewer cristae, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and the nucleus. The tissue culture material revealed similar changes, but showed more virus particles which were located outside the cells, in intracytoplasmic sacs and within the mitochondria. In addition two striking features were observed in the tissue culture material not seen in the human material: a) Budding from the outer mitochondrial membrane into the mitochondrial matrix and b) virus particles attached to the cristae. Since mitochondria are important organelles in the glycolytic-oxidative phosphorylation pathways, perhaps all of us engaged in cancer research should take a closer look at the Warburg effect and carefully consider extranuclear factors operating in oncogenesis.

Acute leukemic cells. Qualitative and quantitative electron microscopy.

Quantitative and qualitative electron microscopic studies were performed on the leukemic cells of 3 patients with stem cell leukemia, 6 patients with acute lymphoblastic leukemia, 7 patients with acute monoblastic leukemia, 3 patients with acute myeloblastic leukemia and 7 patients with acute monomyeloblastic leukemia. Significant quantitative differences were noted between some of the leukemic cells in heterochromatin:euchromatin ratios, cell size, granules per cell, amount of endoplasmic reticulum and the number of polyribosomes. Qualitative abnormalities which were found in some cells of all the leukemic groups were observed. These abnormalities included nuclear pockets, deep nuclear indentations (usually not the stem cell), nucleosomes, dilated perinuclear spaces, centrioles located in nuclear pockets (not in the stem cell or lymphoblast), accumulation of microfibrils (greatest in the monoblast and myeloblast), disrupted mitochondria with virus-like particles (none in stem cells), smaller granules and mitochondrial DNA, glycogen, and myelin whorls. The presence of the smaller granules in disrupted mitochondria and the resulting clear areas is probably related to the deranged carbohydrate metabolism of these cells. The presence of virus-like particles within mitochondria may be extremely important, but requires much more investigation. Some of the above findings may offer clues to further investigation of the acute leukemic cell.