Current Pharmaceutical Biotechnology - Volume 7, Issue 5, 2006

Significant advances in the molecular biology and therapy of hematological malignancies have been made over the last decade. The therapeutic approaches to the hematological malignancies such as acute and chronic leukemias, multiple myeloma, and malignant lymphoma are basically chemotherapy to eradicate the malignant cells. However, severe side effects and complications due to anti-cancer drugs are major pro Read More

Differential methylation of CpG islands is a regulatory mechanism for promoter activity of different classes of genes, including tissue-specific genes. These CpG islands are targets for transformation-associated, aberrant hypermethylation activity during leukemogenesis. Therefore the pharmacological reversion of this methylator phenotype (e.g. by reactivation of tumor suppressor gene expression) is an important ratio Read More

Recent advances in genetic and molecular biology have provided greater insight into the biology of acute myeloid leukemia (AML). These investigations have shown that AML is a heterogeneous disease of biologically different entities. Current therapeutic approaches to AML are based on chemotherapy, but the side effects of the drugs used and various complications, including infections and bleeding, are sometimes fat Read More

Myeloid malignancies are frequently associated with translocations and mutations of tyrosine kinase genes. Fusion genes involving ABL, ARG, PDGFRs, JAK2, SYK, TRKC, and FGFRs, and gain-of-function mutations of FLT3, KIT and JAK2 have been detected at various rates in myeloproliferative disease and acute myeloid leukemia. Furthermore, abnormal overexpression of tyrosine kinases such as FLT3 has als Read More

The IMiDs™ represent a new proprietary class of thalidomide analogues that possess greater potency and less toxicity than the parent compound. As a group, these agents share the pharmacologic property of modulating cellular response to ligand activation, the precise biologic effect of which is cell lineage and stimulant-dependent. Lenalidomide (CC-5013; Revlimid™), a second generation IMiD, has shown significant erythropoi Read More

Currently, patients with acute myeloid leukemia (AML) are treated with cytotoxic chemotherapy and hematopoietic stem cell transplantation (HSCT). With this approach, the majority of patients still die of their disease because of both treatment-related mortality and relapse. Recently, monoclonal antibodies and immunoconjugates have been developed which potentially may increase the efficacy of treatment and decre Read More

Imatinib mesylate, Abl tyrosine kinase inhibitor, has improved the treatment of Bcr-Abl-positive leukemia such as chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). However, resistance is often reported in patients with advanced-stage disease. Several novel tyrosine kinase inhibitors, which have been developed to override imatinib resistance mechanisms such as Read More

Multiple Myeloma (MM) remains an incurable plasma cell malignancy in the bone marrow (BM) despite conventional therapies as well as high-dose therapies with stem cell support. Therefore novel biologically-based therapeutic approaches are required. Recently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in MM. In particular, recognition of the biologic significanc Read More