Arun S. Shet

Chronic myelogenous leukemia: mechanisms underlying disease progression

Chronic myelogenous leukemia (CML), characterized by the BCR-ABL gene rearrangement, has been extensively studied. Significant progress has been made in the area of BCR-ABL-mediated intracellular signaling, which has led to a better understanding of BCR-ABL-mediated clinical features in chronic phase CML. Disease progression and blast crisis CML is associated with characteristic non-random cytogenetic and molecular events. These can be viewed as increased oncogenic activity or loss of tumor suppressor activity. However, what causes transformation and disease progression to blast crisis is only poorly understood. This is in part due to the lack of a good in vivo model of chronic phase CML even though animal models developed over the last few years have started to provide insights into blast crisis development. Thus, additional in vitro and in vivo studies will be needed to provide a complete understanding of the contribution of BCR-ABL and other genes to disease progression and to improve therapeutic approaches for blast crisis CML.

Novel therapies for chronic myelogenous leukemia

The BCR-ABL oncogene is essential to the pathogenesis of chronic myelogenous leukemia, and immune mechanisms play an important role in control of this disease. Understanding of the molecular pathogenesis of chronic myelogenous leukemia has led to the development of several novel therapies, which can be broadly divided into therapies based on 1) inhibition of the BCR-ABL oncogene expression, 2) inhibition of other genes important to the pathogenesis of chronic myelogenous leukemia, 3) inhibition of BCR-ABL protein function, and 4) immunomodulation. We have systematically reviewed each of these novel therapeutic approaches in this article.

Successful liver transplantation in a patient with severe haemophilia A and a high-titre factor VIII inhibitor

Summary.  We present the case of a 61‐year‐old man with severe haemophilia A and a high‐titre factor VIII inhibitor who underwent successful orthotopic liver transplantation (OLT) for hepatocellular carcinoma. Postoperatively, a modest early anamnestic response to FVIII was followed by immunological tolerance to FVIII. This case illustrates the technical feasibility of OLT in some patients with high‐titre inhibitors to FVIII, and suggests that immune tolerance may be induced by endogenously produced FVIII from the transplanted organ.

Intra-Cranial Lesions in a Patient with Hodgkin Lymphoma

Central nervous system (CNS) lesions in newly diagnosed, advanced Hodgkins disease (HD) commonly suggest intracranial involvement with HD. However, occasionally this could be the result of a CNS infection. We report a case of concurrent CNS tuberculosis in a patient with stage III E HD the first reported in the English literature. Management of this case and the literature pertaining to infectious complications of HD are reviewed.