Ahmed Galal, MD, MSc, FRCPC
Fellow in Allogeneic Bone Marrow Transplant,
University Health Network
Princess Margaret Hospital,
Toronto, ON.

Jeffrey Lipton, PhD, MD, FRCPC
Chief, Allogeneic Bone Marrow Transplant Program,
Princess Margaret Hospital,
Head, Chronic Myeloid Leukemia Group,
Associate Professor of Medicine,
University of Toronto,
Toronto, ON.

Introduction
Chronic myelogenous leukemia (CML), in addition to polycythemia rubra vera and essential thrombocytosis, are the most commonly diagnosed forms of the myeloproliferative disorders.^1-5 These diseases share several distinct features:

• They are clonal disorders of hema-topoiesis that arise in a hematopoietic stem or early progenitor cell;
• They are characterized by the dysregulated production of a particular lineage of mature myeloid cells with fairly normal differentiation;
• They exhibit a variable tendency to progress to acute leukemia.

Cytogenetic studies of bone marrow and peripheral blood in the benign myeloproliferative disorders are usually normal. However, CML is invariably associated with an abnormal chromosome known as the Philadelphia chromosome.⁶ CML accounts for 15-20% of adult leukemias. It has an annual incidence of 1 to 2 cases per 100,000, with a slight male predominance.

A dramatic announcement from scientists at a meeting of the American Society of Clinical Oncology may change the lives of patients being treated for chronic myelogenous leukemia (CML). Researchers at Oregon's Health Sciences University have designed a drug that kills cancer cells but does not harm healthy tissues, a common problem with conventional chemotherapy. "What is so dramatic about this new treatment is that it is a pill people take daily", says Dr. Brian Druker, Associate Professor of Medicine. In the tests Druker and his associates conducted, 19 out of 29 patients responded positively to the therapy, with bone-marrow cell abnormalities reduced to 15% or less.

CML is a malignant hematologic disorder that predominantly affects the middle-aged and elderly. In 95% of CML cases there is an acquired reciprocal translocation of chromosomes 9 and 22 which results in a hybrid known as the Philadelphia chromosome. This Ph chromosome contains various portions of the breakpoint cluster region (BCR) and the ableson murine leukemia virus (ABL) genes. The two sets of genes are transcribed by the same promoter and eventually translated into a fusion protein that functions as an intracellular tyrosine kinase. This tyrosine kinase is involved in promoting cellular proliferation and inhibiting apoptosis and confers a survival advantage on malignant stem cells.

The new drug, called STI-571, targets the white blood cells and inhibits the BCR-ABL tyrosine kinase pathway. So far there appear to be no adverse side effects.