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Chronic myelogenous leukemia

Chronic myelogenous leukemia (or CML) is a form of chronic leukemia characterised by increased production of myeloid cells in the bone marrow. It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation termed the Philadelphia chromosome. It is traditionally treated with chemotherapy, interferon and bone marrow transplantation, although a specific inhibitor (imatinib mesylate) has radically changed the management. more...

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Signs and symptoms

Patients are often asymptomatic at diagnosis, presenting incidentally with an elevated white blood count on a routine laboratory test. Symptoms may include: malaise, low grade fever, increased susceptibility to infections, anemia and thrombocytopenia with resultant bruising (although an increased platelet count, thrombocytosis, may be a feature). Splenomegaly may also be seen.

The disease may remain dormant for years, but a proportion proceed to accelerated phase (in which the diseases progresses rapidly) or overt blast crisis, which has the symptoms and risks of acute myelogenous leukemia (AML).

Diagnosis

CML is often suspected on the basis on the full blood count, which shows increased granulocytes of all types (including basophils). When the index of suspicion is high, a bone marrow biopsy is required to distinguish CML from other diseases that feature the same symptoms.

Ultimately, CML is diagnosed by detecting the Philadelphia chromosome (a translocation between the 9th and 22nd chromosome leading to an aberrant protein that drives cell division). This translocation leads to bcr-abl fusion and activation of protein tyrosine kinase cascade.

Disease activity can be determined on the basis of the bone marrow examination, cytogenetics and by quantitative PCR.

Pathophysiology

CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation named Philadelphia chromosome, in 1960. The fusion of two genes on chromosomes 9 and 22, termed abl and bcr respectively, leads to a protein that propels mitosis and causes genomic instability (leading to further mutations).

CML progresses to accelerated phase, and then blast crisis, when additional genetic abnormalities speed up the rate at which new malignant cells are produced in the bone marrow. A second Philadelphia chromosome may appear, as well as deletions of (parts of) chromosomes.

Epidemiology

CML occurs in all age groups, but most commonly in the middle-aged and elderly. Its annual incidence is about 1 per million.

Treatment

Chronic phase

Chronic phase CML is treated with imatinib (marketed as Gleevec or Glivec; previously known as STI-571). In the past, hydroxyurea, alkylating agents (e.g. cytarabine), interferon alfa 2b and steroids were used, but this has been replaced by imatinib. Imatinib is a new agent which specifically targets the abnormality caused by the Philadelphia chromosome. It is better tolerated and more effective than previous therapies. Bone marrow transplants were also used as initial treatment for CML before imatinib and can be curative. In patients who fail to achieve a cytogenetic remission with imatinib or who relapse while on imatinib, a bone marrow transplant should be considered.

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Medical Management of Chronic Myelogenous Leukemia (Basic and Clinical Oncology , Vol 16) $10.99 Myelogenous Leukemia: First try alpha interferon; Allogeneic stem cell transplants might be avoidable, can be safely delayed. (Better Survival, Less Morbidity). ... : An article from: Internal Medicine News $5.95
Chronic Myelogenous Leukemia (Hematology) $18.99 Chronic Myelogenous Leukemia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References $48.95
Management of molecular-targeted therapy for chronic myelogenous leukemia : An article from: Journal of the American Academy of Nurse Practitioners $20.00 Chronic Myelogenous Leukemia $55.06
Acute Leukemias IX $133.33 Cytogenetic evolution in chronic myelogenous leukemia: Relation of chromosomes to progression and treatment of the disease
Granulocytic colony stimulating activity in plasma and in leukocytes obtained from normal and from chronic myelogenous leukemia patients / Myra Louise Patchen

Leukemia overpowers drug in two ways - STI-571 and chronic myelogenous leukemia - Brief Article
The medicine known commercially as Gleevec serves as a powerful weapon for people fighting the blood cancer called chronic myelogenous leukemia, or CML. Although the drug appears to cure many patie
Bilateral alveolar infiltrates in a 29-year-old man with chronic myelogenous leukemia - pulmonary and critical care pearls
A 29-year-old man had received a diagnosis of chronic myelogenous leukemia (CML) 6 years before presentation. He had not undergone bone marrow transplantation ...
Nutritional support for chronic myelogenous and other leukemias: a review of the scientific literature - Leukemia
Abstract Chronic myelogenous leukemia (CML) is a slowly progressive disease characterized by the overproduction of granulocytes (neutrophils, eosinophils, ...
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A 38-year-old black man with known sickle cell anemia and multiple episodes of painful crises was admitted to our hospital with chief complaints of severe ...
New Drug Thwarts a Chronic Leukemia - STI-571 - Brief Article
In 1960, two Philadelphia-based researchers, Peter C. Nowell and David A. Hungerford, found an odd chromosome lurking in the cancer cells of people with chronic myelogenous leukemia. It was the fir
A unique, complex variant Philadelphia chromosome translocation in a patient with typical chronic myelogenous leukemia
The Philadelphia (Ph) chromosome [der(22) t(9;22) (q34;q11)] is the characteristic chromosomal abnormality found in chronic myelogenous leukemia (CML).
Chronic myelogenous leukemia
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder arising from neoplastic transformation of pluripotent stem cells and is characterized ...
Stopping a killer with interferon? - chronic myelogenous leukemia
Stopping a killer with interferon? By name alone, chronic myelogenous leukemia (CML) might not sound as serious as acute leukemia. But CML moves quickly ...

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