Rakesh Biswas MD Professor, Medicine, People's College of Medical Sciences, Bhopal, India Lecture first conceived and delivered to medicine undergrads in Melaka Manipal Medical College, Manipal University, Melaka, Malaysia. Chronic Myeloid Leukemia

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The clinical manifestations of Chronic Myeloid Leukemia ( CML) are insidious and are often discovered incidentally when an elevated White Blood Cells (WBC) count is revealed by a routine blood count or when an enlarged spleen is revealed during a general physical examination. Source: E-medicine

3 clinical phases 1) Initial chronic phase 2) Accelerated phase 3) Blast crisis Most patients are diagnosed while still in the chronic phase.

Myelosuppressive therapy, was formerly the mainstay of treatment to convert a patient with CML from an uncontrolled initial presentation to one with hematologic remission and normalization of the physical examination and laboratory findings

Hydroxyurea (Hydrea), an inhibitor of deoxynucleotide synthesis, is the most common myelosuppressive agent used to achieve hematologic remission. The initial blood cell count is monitored every 2-4 weeks, and the dose is adjusted depending on the WBC and platelet counts.

CML accounts for 20% of all leukemias affecting adults Increased incidence was reported among individuals exposed to radiation in Nagasaki and Hiroshima after the dropping of the atomic bomb. The presence of BCR/ABL rearrangement is the hallmark of CML,

CML is an acquired abnormality that involves the hematopoietic stem cell. It is characterized by a cytogenetic aberration consisting of a reciprocal translocation between the long arms of chromosomes 22 and 9; t(9;22).

The translocation results in a shortened chromosome 22, an observation first described by Nowell and Hungerford and subsequently termed the Philadelphia (Ph) chromosome after the city of discovery.

The Philadelphia chromosome Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q (c-abl to a specific breakpoint cluster region [bcr] of chromosome 22 indicated by the arrows

This translocation relocates an oncogene called abl from the long arm of chromosome 9 to the long arm of chromosome 22 in the BCR region.

A new approach to treatment of this disease is to directly inhibit the molecular cause of the disease. …using a protein-tyrosine kinase inhibitor that inhibits the bcr-abl tyrosine kinase

The 3-fold goals of treatment for CML have changed markedly in the past 10 years; a) Hematologic remission (normal CBC, no organomegaly), b) Cytogenetic remission (normal chromosome 0% Ph-positive cells), and, most recently, c) Molecular remission (negative PCR result for the mutational BCR/ABL m-RNA). The latter is an attempt for cure and prolongation of patient survival.