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The key nuclear export protein CRM1/XPO1 may represent a promising novel therapeutic target in human multiple myeloma (MM). Here we showed that chromosome region maintenance 1 (CRM1) is highly expressed in patients with MM, plasma cell leukemia cells and increased in patient cells resistant to bortezomib treatment. CRM1 expression also correlates with increased lytic bone and shorter survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel, oral, irreversible selective inhibitors of nuclear export (SINEs) targeting CRM1 (KPT-185, KPT-330) induce cytotoxicity against MM cells (ED50

The failure of conventional chemotherapy to eradicate chronic lymphocytic leukaemia cells and induce cure has led many clinicians to investigate the use of high dose chemotherapy and haemopoietic stem cell rescue in this disease. The selection of patients remains a major problem because this is a disease of elderly patients with a median overall survival of 7 years and will only therefore be applicable to a minority of patients. However transplantation is the most likely therapeutic option at this time to lead to cure in this condition. The best type of transplant is not known and not all patients will be able to mobilise adequate numbers of stem cells or have a suitable donor identified. Autologous transplantation relies on the ability of high doses of chemotherapy to eradicate disease whilst allogeneic transplantation attempts to harvest the graft versus leukaemia effect that has been identified in chronic granulocytic leukaemia. However, the high treatment related mortality and morbidity of allogeneic transplants has led to interest in the use of non-myeloablative allografts which hope to maximise the immunological effects of transplantation to achieve durable remissions. To date there have been no randomised clinical trials to compare the efficacy of combination chemotherapy, autologous or allogeneic transplants and this is unlikely to happen in the near future. Other issues that need to be addressed include the timing of transplantation, the source of stem cells, the optimal conditioning regimen and the role of immunomodulation post transplantation. This review attempts to answer some of these questions.

Tests for folate and vitamin B12 deficiency are frequently requested by clinicians in many different specialties. An audit of folate assay methodology was undertaken to establish the number of tests and types of assay performed in different centres, and to analyse the indications for these investigations, with a view to advising on the most appropriate assay for use in the laboratory. A questionnaire was sent to 30 centres, 24 (80%) of which participated in the audit. The types of folate assay performed, number of requests, reference range and method of analysis differed between centres. The major specialty users of the service were general practitioners, general physicians and geriatricians. A detailed analysis of 1,259 consecutive requests for folate assays from a single representative laboratory showed a significant correlation between serum and red cell folate levels (r = 0.49, p < 0.001). However, in patients with low serum folate, there was no correlation with red cell folate in the absence of macrocytosis. The major indication for folate analysis was for haematological abnormalities but 36% of cases were for nonspecific indications. A haematologist with an interest in folate metabolism was invited to moderate the results at an audit meeting of haematologists. The consensus was that the most appropriate screening test for folate deficiency is the serum assay, which can be combined easily with vitamin B12 assay.

The intracytoplasmic inclusions seen in most cells from a patient with B prolymphocytic leukaemia were analysed using both light and electron microscopy. They consisted of a dense homogeneous structure and were surrounded by a membrane, which had no continuity with the Golgi cisternae or the endoplasmic reticulum; some inclusions had a clear association with small lysosomal granules. Immunofluorescence and immunoperoxidase studies using light microscopy failed to elucidate completely the nature of the inclusions, but immunocytochemical reactions performed using electron microscopy suggested an immunoglobulin nature. All inclusions were negative for acid phosphatase and periodic acid Schiff. The nature of the inclusions described in the prolymphocytes of this patient were compared with those previously recorded in B prolymphocytic leukaemia.