muramidase and Leukemia--Myelomonocytic--Acute

We report a case of primary acute myelomonocytic leukemia involving the bone marrow that resembled sarcomatoid carcinoma. The neoplastic cells in bone marrow biopsy specimens formed cohesive-appearing clusters and cords separated by an immature fibroblastic proliferation and myxoid stroma. Blasts in the bone marrow aspirate smears formed clusters and sheets, and a subset of blasts exhibited erythrophagocytosis. Dysgranulopoiesis was also present. Lineage was confirmed by immunohistochemical analysis of formalin-fixed, paraffin-embedded tissue. The tumor cells showed strong reactivity for lysozyme, myeloperoxidase, CD45, and CD68 and were negative for keratin, S100, CD20, and CD3. The serum lysozyme concentration (110 microgram/mL) was 13 times greater than the normal value (8 microgram/mL). Cytogenetic studies performed on bone marrow aspirate material revealed a complex karyotype, including trisomy 8 and abnormalities of chromosome 11q. We report this case of acute myelomonocytic leukemia because the neoplastic cells appeared cohesive and spindled, resembling sarcomatoid carcinoma, and therefore caused diagnostic difficulty. Other monocytic neoplasms with similar resemblance to carcinoma or sarcoma have been reported in the literature, suggesting that the tendency to appear cohesive may be an inherent characteristic of neoplastic cells with monocytic differentiation.

Topics: Biomarkers, Tumor; Bone Marrow; Bone Marrow Neoplasms; Carcinosarcoma; Cytarabine; Cytogenetics; Diagnosis, Differential; Fatal Outcome; Humans; Idarubicin; Immunohistochemistry; Leukemia, Myelomonocytic, Acute; Male; Middle Aged; Muramidase

Using an ultrastructural immunogold method, we performed a quantitative study on cellular lysozyme (LZ) content in young normal bone marrow cells and in 14 cases of acute myeloid leukaemia (AML) of the M2, M3, M4 and M5 types. In five cases of M2 we found significantly lower LZ content than in normal promyelocytes and than in nine cases of M3, M4 and M5. In M3, M4 and M5 cells a very high LZ content was observed whereas the serum LZ activity was high in M4 and M5 and normal in M3. The intragranular LZ content was especially high in M5 and in most granules of M4 cells. The immunogold reaction (IGR) for LZ was also performed in cells previously reacted for myeloperoxidase (MPO). In M2 the granules showed definite positive MPO reactivity and low LZ density (granulocytic pattern), whereas in M5 we found high granular LZ content and weak or almost negative MPO activity (monocytic pattern). In M4 we found 'granulocytic' and 'monocytic' type of granules in the same cell. The IGR for LZ performed in post-embedded M5 cells which were previously subjected to phagocytosis of latex particles, showed granules that had moved toward the phagosome, releasing LZ without degranulation. The above findings and those showing normal serum LZ in M3 despite their high cellular LZ content, definitely indicate that only leukaemic M4 and M5 cells secrete LZ into their environment, explaining the high serum LZ observed in those leukaemias.

Topics: Acute Disease; Bone Marrow; Gold Colloid; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Microscopy, Electron; Muramidase; Peroxidase; Phagocytosis

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL-4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Adult; Antigens, Surface; Cell Adhesion; Cell Differentiation; Cell Line; Chromosome Banding; Culture Techniques; Cytokines; Eosinophilia; Humans; Isoquinolines; Karyotyping; Kinetics; Leukemia, Myelomonocytic, Acute; Macrophages; Male; Microscopy, Electron; Muramidase; Phagocytosis; Piperazines; Protein Kinase C