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Epidemiology
• Accounts for 15% of adult leukemias
• Incidence of 1-2 cases per 100 000 population
Chronic Myelogenous Leukemia • Male-to-female ratio of 1.3 to 1
• Incidence increases with age
Chronic Myeloid Leukemia • Median age at presentation is 45 to 55 years
Chronic Granulocytic Leukemia

Definition Philadelphia Chromosome

• Chronic myeloid leukemia (CML) is a pluripotent
stem cell disease characterized by:
– anemia
– extreme blood granulocytosis and granulocytic immaturity
– basophilia
– thrombocytosis
– splenogemaly
– reciprocal translocation between chromosomes 9 and 22
– Inevitable transition from a chronic to an accelerated
phase and on to blast crisis

• The clinical course may be characterized by Risk factors

three separate phases
– Chronic phase, which is generally controllable with
chemotherapeutic agents and lasts 2 to 5 years
• DNA topoisomerase II inhibitors
– Accelerated phase, which lasts approximately 6 to
18 months; • exposure to very high doses of ionizing
– Blastic (acute) leukemia phase, which lasts 3 to 4 radiation
months and is generally unresponsive to
treatment

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The Ph Chromosome

Pathophysiology

Molecular Basis of CML

ABL gene BCR gene

BCR-ABL gene Structure of BCR-ABL Fusion Protein

Molecular Consequence of t(9;22)

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Mechanism of BCR-ABL mediated Mechanisms implicated in the

malignant transformation pathogenesis of CML

Characteristics of Patients with

Chronic Myeloid Leukemia at
Presentation
• Clinical findings
– Fatigue, anorexia, weight loss
– Splenomegaly
– Hepatomegaly
• Peripheral-blood findings
– Elevated WBC > 25,000/mm3
– Elevated platelet count in 30 to 50% of cases
– Basophilia
– Reduced leukocyte alkaline phosphatase activity
– All stages of granulocyte differentiation visible on
peripheral smear

Faderl, S. et. al. Ann Intern Med 1999;131:207-219

Peripheral blood and bone marrow in CML

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Characteristics of Patients with

Chronic Myeloid Leukemia at
Presentation
• Bone marrow findings
– Hypercellularity, reduced fat content
– Increased ration of myeloid to erythroid cells Therapy for CML
– Increased number of megakaryocytes
– Blasts and promyelocytes constitute less than 10
percent of all cells

Milestone in the Treatment of CML Imatinib mesylate

• 1856 – Arsenicals (Fowler’s solution)
• Prior to 1950s – Total-body or splenic
radiation therapy
• 1950s – Busulfan
• 1972 – Hydroxyurea
• 1990s- Interferon α with or without cytosine
arabinoside

Figure 1. An operational classification of hematologic malignancies

Allogeneic stem cell transplantation

Tefferi, A. Oncologist 2003;8:225-231

Copyright ©2003 AlphaMed Press