Plasma cell leukaemia

Plasmocytoma Extramedullary plasmocytic lymphoma likewise has its origin in immunoglobulin-secreting B-lymphocytes. It is also termed multiple myeloma. The condition occurs most frequently in 7 decade of life and ends fatally after 1-2 (-3) years. In the liver, there are sometimes sinusoidal and portal infiltrations of B-lym-phocytes and plasmocytic tumour cells nodular formation can also occur. Generally, however, liver involvement is found in 40% of cases. (47, 61) (s. fig. 38.12) Recently, patients with non-response or relapse after high-dose chemotherapy were treated successfully with thalidomide (starting with 200 mg daily, the dose was increased by 200 mg every two weeks until it reached 800 mg per day). (48, 56) Plasma cell leukaemia is a rare complicative variant which tends to have its own individual course. 

Acronycine (57), isolated in the Lilly laboratories from different Acronychia spp. (Rutaceae), has shown the broadest experimental tumour activity of any alkaloid studied. It was first isolated from Acronychia baueri Its activity against C-I498 myelogenous leukaemia, X-5563 plasma cell myeloma, and adenocarcinoma 755 was found by the Lilly group.Acronycine has been obtained by different syntheses however, no evidence for clinical trials with acronycine has yet been found in the literature. 

A homogeneous glycoprotein (mol. wt. 2.7 x 10 ) has been recovered in significant concentrations from the urine of patients with plasma cell leukaemia. ... 

Human LICR-LON-HMy-2 Human plasma cell leukaemia — 5... 

Bethlenfalvay, N. C., Henley, L. B., Rupp, T. D. and Phyliky, R. L. (1976) Nonsecretory plasma cell dyscrasia followed by acute granulocytic leukaemia 25 years after thorotrast administration. Cancer, 37, 1449. 

Physiologically, these plasma changes are included here since they reflect impaired numbers or function of B-lymphocytes. Two broad categories are recognizable. First, such immunodeficiency states may exist on congenital basis and often do so with concurrent defects in the T cells (Fig. 1). Alternatively, severe reductions in immunoglobulin levels often develop in the course of chronic lymphocytic leukaemia and myeloma. Not dissimilar impairment of immune competence is found with nephrotic syndrome, protein-losing enteropathy or even malnutrition, and in these instances is equally profound. 

IC50 (nM) (Leukaemia cells CCRF-CEM) 3.2 Plasma half life (min) (mice) 212 88... 

Phase I and II clinical trials indicated that acronycine reduced pain of the spine in some patients with multiple myeloma [280,282,283]. Acronycine has been reported to cause leukopoenia and to have CNS-depressant activity [284], Biochemically, acronycine inhibits incorporation of extracellular nucleosides into the RNA and DNA of leukaemia L-5178Y cell culture. There is, however, no evidence of interaction between acronycine and DNA or inhibition of template activity of DNA. This alkaloid does not inhibit nucleic acid synthesis in the cell, but rather inhibits the accumulation of extracellular uridine or thymidine, as nucleotides, in the intracellular precursor pool [285, 286], Acronycine, acting primarily on membranous organelles [287], seems to interfere with the structure, function and/or turnover of cell membrane components, thereby changing the fluidity of the plasma membrane [288]. 

Copper metabolism has been studied in a variety of neoplastic diseases [332]. It is now known that patients with acute leukaemia have elevated serum or plasma copper concentrations [333]. The elevation in serum copper correlated with an increase in number of bone marrow blast cells. A decline in symptoms or remission of disease following therapy correlated with a decrease in serum copper concentration [332-335], enabling accurate prognoses based upon serum copper determinations. 

The products of the major histocompatibility locus have been shown to interact with viral antigens on the cell surface of thymocytes. A number of polypeptides bind to the major envelope glycoprotein of Rauscher murine leukaemia virus. The receptors for this glycoprotein, which probably involve lipoproteins, have been prepared from plasma membrane preparations from mouse cells. ... 

In much the same way, a cultured line of lymphoblasts, from lymphatic leukaemia in the mouse, became resistant to methotrexate through a decrease in the transport of this drug, effected by modifying the plasma membrane (Hill et aL, 1979). It was already known that, in mouse leukaemia, the survival time of the leukaemic cell suspensions is inversely proportional to the rate of uptake of methotrexate (. 7), but this rate begins to decline soon after treatment is instigated (Kessel et aL, 1965). This phenomenon has not been demonstrated in human leukaemia. 

P Gimsing. Cobalamin forms and analogues in plasma and myeloid cells during chronic myelogenous leukaemia related to clinical condition. Br J Haematol 89 812-819, 1995. 

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