Antigenic phenotype of the myeloid leukaemic cells defined by monoclonal antibodies

The antigenic characteristics of the leukaemic cell population in 31 patients with acute myeloid leukaemia (AML) and 5 patients with acute undifferentiated leukaemia (AUL) was investigated using a panel of 15 monoclonal antibodies (Mc Abs). We chose 14 Mc Abs that react with lineage--and stage related myeloid antigens and L243 Mc Ab that reacts with HLA-DR antigen. In AML cases we correlated the antigenic phenotype with morphological FAB classification. The study indicates a substantial antigenic heterogeneity of the surface antigen expression on leukaemia cells particularly in M1, M2 and M4 AML cases. The morphological subtype of these leukaemias tended to correlate with the immunologic phenotype, particularly in more differentiated AML cases such as M3 or M5. The most immature cell phenotype characterised "undifferentiated" AML, which was expressed by the reactivity or L243, BI3C5, MY9, VIM-2 and S3-13 Mc Abs with the majority of the patients. The analysis shows that although there is a tendency for the morphology to correlate with the surface antigen phenotype each morphological group contains patients having different surface antigen phenotype.     

Antigenic phenotype of chronic granulocytic leukaemia progenitor cells in chronic phase and in blastic transformation characterized by means of monoclonal antibodies

We studied the surface antigens of "early" and "late" granulocyte-macrophage progenitor cells (CFU-GM) from bone marrow and peripheral blood of 18 patients with chronic granulocytic leukaemia in chronic phase (CGL-CP) using 14 selected murine monoclonal antibodies (McAbs) in complement dependent cytotoxicity assay followed by culture in methyl cellulose. The same panel of McAbs was used to determine the antigens on leukaemic blast cells from peripheral blood of 15 patients with CGL in blastic transformation (BT) by complement mediated lysis and in vitro culture technique for clonogenic blasts (CFU-L) and immunofluorescence assay for total blast population. McAb for HLA-DR antigens (L243) and McAbs MY9, S3-13, S17-25 and 53/6 reacted with CFV-GM and CFU-L. In contrast, McAbs PM81 and AML-2-23 recognizing antigens on more mature myeloid cells did not react with these progenitor cells. McAb S4-7 reacted with the majority of CFU-L and a small proportion of "early" and "late" CFU-GM. This McAb may be useful for the prediction of blastic transformation in CGL patients. Generally, the reactivity of most McAbs was more heterogeneous with CFU-L than with CFU-GM in individual patients. The majority of McAbs included in our study reacted with a higher percentage of CFU-L and CFU-GM than predominant blast cell population in individual patients perhaps because the detected antigens are expressed more strongly on dividing progenitors than on relatively nonproliferative progeny. Thus we interpret the results of these studies showing that the antigenic phenotypes of the blast colony progenitor cells in CGL-BT are very similar to but not identical with those of CFU-GM from CGL-CP patients.     

The influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine on normal and chronic myelogenous leukemia granulocyte-macrophage progenitor cells in vitro

We evaluated the influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal and chronic myeloid leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in semisolid culture in vitro. Amifostine at a concentration of 1 mg/ml was either added directly to the culture medium of normal and CML CFU-GM, or mononuclear cells (MNCs) were first preincubated with amifostine at the same concentration, washed in Iscove's modified Dulbecco minimum essential medium (IDMEM) and then added to the culture medium. Amifostine used alone inhibited the growth of CML CFU-GM colonies to a higher degree than those of normal CFU-GM, but the differences were not statistically significant. Amifostine preincubated with MNCs and used together with the highest concentration of 2-CdA significantly inhibited the colony growth of CML CFU-GM as compared to 2-CdA alone (p<0.05). In contrast, the colony growth inhibition of normal CFU-GM was not significantly lower compared to 2-CdA used alone. Our studies suggest that 2-CdA used together with amifostine is more toxic to leukemic CFU-GM than to their normal counterparts.     

Adenosine release upon spinal cord injury

The hypothesis that release of adenosine following spinal cord injury (SCI) may provide neuroprotective feedback is explored. Consistent with this hypothesis, substantial release of adenosine, estimated to reach 100 microM in the extracellular space, was detected by microdialysis sampling immediately following contusion SCI. There is also considerable release of excitatory amino acids following SCI. The latter was not affected by administration of the general adenosine receptor antagonist theophylline and the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine, implying that the adenosine released following SCI does not significantly influence the release of neurotoxic amino acids. Administration of the concentration of glutamate released upon SCI into the spinal cord caused only about 1% as much release of adenosine as did injury, evidence that elevated excitatory amino acids do not elicit an appreciable fraction of the release of adenosine that follows SCI. Results obtained suggest that release of endogenous adenosine is not neuroprotective by blocking release of excitatory amino acids following SCI.     

Pituitary-adrenocortical responses to the chronic administration of granulocyte colony-stimulating factor in rats

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, but it may play a role in the regulation of the neuroendocrine system activity. Only few data are available about its possible influence on the pituitary gland. We have recently reported an acute stimulatory effect of G-CSF (and of GM-CSF) on adrenocorticotropic hormone (ACTH) secretion in rats in vivo. The purpose of the present study was to evaluate whether chronic administration of G-CSF affects ACTH and corticosterone secretion and growth processes of the rat anterior pituitary gland and adrenal cortex in vivo. We have demonstrated that G-CSF (at a dose of 10.0 microg/kg body weight (BW)) injected s.c. once daily (for 7 days), stimulated both ACTH and corticosterone secretion. Simultaneously, G-CSF treatment did not change the total anterior pituitary cell proliferation as revealed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). On the other hand, proliferative activity of corticotrophs, detected in the sections of the anterior pituitary using double-labeling. was significantly increased after treatment with G-CSF. Moreover, this growth factor induced an increase in the proliferation ratio in the entire adrenal equatorial section. These findings suggest an involvement of G-CSF in the regulation of pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune system and the endocrine glands.     

Diagnostic and therapeutic quandaries in primary manifestation of Hodgkin's disease in the central nervous system

We report the case of a 23-year-old female with severe neurologic dysfunction without a clear cause at the time of initial presentation. The search for an underlying malignancy revealed a slightly enlarged cervical lymph node with Hodgkin's disease (HD). There was no evidence of a brain tumor despite nonspecific bright changes in proton density in the basal ganglia of the right hemisphere of the cerebellum, right cerebellar tonsil, posterior limb of the internal capsule, and the right side of the medulla spinae as shown by magnetic resonance imaging (MRI) as well as reactive lymphocytosis with slightly elevated protein levels in the cerebrospinal fluid (CSF). The findings suggested a cerebellar disorder, with main differential diagnosis between neurologic paraneoplastic syndrome (NPS) and HD involving the CNS. Based on limited experience with NPS and HD in the CNS, possible diagnostic and therapeutic options are discussed.     

CD38 gene polymorphisms and genetic predisposition to multiple myeloma

Single nucleotide polymorphisms (SNPs) of adhesion and signaling genes may influence the etiopathogenesis of multiple myeloma (MM). CD38 molecule and its ligand CD31 are expressed and interact in malignant plasma cells and MM microenvironment. In this study we evaluated allele frequencies and distribution of two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg¹⁴⁰Trp) in 175 Caucasian patients with MM and 207 healthy blood donors. The carriers of variant G allele of the rs6449182 SNPs were found to have significantly elevated risk of MM as compared to non-carriers; odds ratio = 5.69 (95% confidence interval = 3.7–8.7), p < 0.0001. In contrast, rs1800561 SNP minor T allele was detected at very low and comparable frequencies in patients and controls groups. In conclusion, our data suggest that inherited genetic variation in CD38 gene may impact on the risk of MM development.