No abstract

W E describe a patient with a unique mantle-cell lymphoma, with cycles of acute illness alternating with spontaneous remissions. During the acute phase the patient had fever, generalized lymphadenopathy, hepatosplenomegaly, increased liver-enzyme concentrations, leukocytosis, and thrombocytopenia. These bouts remitted after two to three weeks without treatment. Fifteen such cycles were documented over a period of 50 months.During the acute phase blast-like B lymphocytes in the blood expressed surface IgM, IgD, and CD5, whereas during clinical remission a small population of IgM and CD5 ϩ lymphocytes persisted. Two B-cell clones with differently rearranged heavy-chain genes consistently appeared in the blood during the recurrent acute phases. During the spontaneous remissions, one clone (termed the "acute clone") regressed while the second clone remained relatively stable. These findings suggest that proliferation and death of the acute-clone cells determined the cyclic nature of the disease. The lymphoma cells of the acute phase, but not those of remission, were shown to undergo spontaneous apoptosis in vitro. This process was enhanced by inhibitors of messenger RNA and protein synthesis, suggesting that it was regulated by preexisting factors with short halflives. No molecular alterations were demonstrated in bcl -2 and p53 genes, which are known to regulate apoptosis. C ASE R EPORTA 61-year-old man was hospitalized in March 1990 because of a high fever, perspiration, abdominal pain, and vomiting of one week's duration. Physical examination revealed generalized lymphadenopathy, splenomegaly (spleen palpable 3 cm below the costal margin), and hepatomegaly (liver tip palpable 5 cm below the costal margin). Laboratory tests revealed a hemoglobin level of 14 g per deciliter, leukocytosis (68,000 leukocytes per cubic millimeter), and a platelet count of 44,000 per cubic millimeter. The differential white-cell count showed 12 percent segmented and 88 percent mononuclear cells, 70 percent of which were blast-like, with large cleaved nuclei and prominent nucleoli. Examination of the bone marrow showed heavy infil-tration by the lymphoid cells with the same morphologic features. A lymph-node biopsy revealed intermediate-grade malignant lymphoma of the diffuse mixed, predominantly small-cleaved-cell type. Cellsurface markers of peripheral mononuclear cells showed that 80 to 90 percent were B cells expressing IgMk and CD5 but not CD10. The diagnosis of mantle-cell lymphoma was established. The t(11;14) translocation, common in mantle-cell lymphoma, 1 was not detected.The bilirubin concentration was 2.8 mg per deciliter (48 m mol per liter), the serum uric acid concentration was 9.6 mg per deciliter (571 m mol per liter), the blood urea nitrogen concentration was 56 mg per deciliter (20 mmol per liter), and liver-enzyme levels were substantially increased. Serologic tests for Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, human T-cell lymphotropic virus type I, herpesviruses 1 and 6, and hepatitis A, B, ...

It has been recently shown that mutations in both of the recombination activating genes RAG1 and RAG2 are involved in each of the two different types of severe combined immunodeficiency (SCID) syndromes: T-B- SCID and Omenn's syndrome (OS). The objective of the study was to search for novel mutations in the RAG genes and to offer prenatal diagnosis for families that have been identified as at risk of T-B- SCID or OS. Mutation analyses of polymerase chain reaction products of RAG1/RAG2 genes were performed in 14 cases (T-B- SCID = 6 and OS = 8). Consanguinity was reported in seven (50%) families. Four missense mutations in the RAG2 gene in six of eight OS patients and in four of six T-B- SCID patients were detected. The C1845T transition leading to a Tre215Ile substitution is a novel mutation. All but one of the patients were homozygous for the detected mutations, possibly reflecting the consanguinity in these families and the relative rarity of the disease-causing mutations. In addition, three putative polymorphic sites were found. Prenatal diagnosis was offered to seven families, but three of them declined genetic counseling for religious reasons. In the remaining families, four pregnancies were successfully completed, and in one case, the family chose to have an abortion because of a homozygous mutation. Mutations in RAG1/RAG2 genes were detected in only some of the T-B- SCID or OS patients, and the molecular basis for the remaining cases has yet to be elucidated. Important factors such as religious beliefs need to be considered when offering prenatal diagnosis to certain families.

Molecular remission according to FISH and multiplex RT-PCR can be achieved by imatinib within 1 yr of therapy. There is a good correlation between the FISH, multiplex and RQ-PCR results in terms of the kinetics of disappearance of the BCR-ABL transcript and the predictability of each method for the other. Although RQ-PCR is the most sensitive method for molecular follow-up, FISH and multiplex RT-PCR can be used as complementary tools, at least during the early period of treatment.

A rare case of CNS Burkitt's lymphoma presenting as acute Guillain-Barré syndrome is presented. A 6-year-old previously healthy female presented with acute onset of limb and truncal weakness, involvement of ocular and bulbar nerves, and areflexia. The clinical diagnosis of Guillain-Barré syndrome prompted treatment with intravenous gammaglobulin with no response. A lumbar puncture following revealed marked pleocytosis, elevated protein, and decreased glucose. Immunological, cytological, and molecular studies of these cells confirmed the diagnosis of Burkitt's lymphoma IgM, kappa with t(8;14) and rearrangement of the J and kappa immunoglobulin chains. Aggressive systemic and intrathecal chemotherapy were started and within 5 days remission was achieved. The child is in complete remission 2 years from diagnosis. Although very rare, CNS lymphoma should be taken into account in every patient presenting with the clinical features of acute polyneuropathy.

No abstract

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor suppressor genes. However, the investigation of genomic instability of microsatellites has disclosed a new mechanism for human carcinogenesis, which is involved not only in hereditary nonpolyposis colon cancer (HNPCC) but in a number of other malignancies as well. To determine whether microsatellite instability is involved in Hodgkin's disease, we screened 16 such tumors using 7 microsatellite marker loci on 6 chromosome arms 4, 5, 9p, 9q, 11, 14, and 17. Using the polymerase chain reaction method, DNA samples from the tumors and from normal peripheral blood leukocytes from each patient were compared for the allelic pattern produced at each locus. Five cases of genomic instability were identified, suggesting that this mechanism is relevant to the pathogenesis of HD.

Five patients with clinical and laboratory features typical for juvenile chronic myeloid leukaemia (JCML) are presented. Rearrangement of the j joining region of the immunoglobulin heavy chain (Jh) was demonstrated in three children out of five analysed. As no Vh to DhJh nor kappa light chain rearrangements were demonstrated, it is reasonable to speculate that the transforming event of the stem cell happened at the stage when Dh to Jh rearrangement took place. As the monocytic lineage is prominent in JCML, it is suggested that the transforming event happens in a unique stem cell with intermediate differentiation towards the myelomonocytic as well as the B-lymphatic lineage. This stem cell, which is present at a certain stage of embryogenesis, disappears later. Such an early 'hybrid' cell is sometimes involved in leukaemias of early infancy, and may be the transformed cell in some cases of infantile leukaemia.