“Chronic myeloid leukaemia BCR‐ABL1+ (CML) is a clonal disorder of a pluripotent stem cell”.
- The disease accounts for around 15% of leukaemias and may occur at any age.
- The diagnosis of CML is rarely difficult and is assisted by the characteristic presence of the Philadelphia (Ph) chromosome. This results from the t(9;22) (q34;q11) translocation between chromosomes 9 and 22.
- The abnormal chromosome 22 is the Ph chromosome.
Leukemoid reaction:
“Dramatic elevation of granulocytic count in response to infection, stress, chronic inflammation and certain neoplasms”.
Pathogenesis:
CML is always associated with the presence of BCR-ABL fusion gene (ph
chromosome).
- BCR-ABL gene is the product of balanced (9;22) translocation that moves ABL from ch 9 to position on ch 22 adjacent to BCR.
- BCR-ABL fusion gene is present in granulocytic, erythroid, megakaryocytic, and Bcell precursors.
- Ph chromosome is highly characteristic of CML.
Clinical Features:
This disease occurs in either sex (male: female ratio of 1.4 : 1), most frequently
between the ages of 40 and 60 years.
- However, it may occur in children and neonates, and in the very old.
- In up to 50% of cases the diagnosis is made incidentally from a routine blood count.
- In those cases where the disease presents clinically, the following features may be seen:
- Symptoms related to hypermetabolism (e.g. weight loss, lassitude, anorexia or night sweats).
- Splenomegaly is nearly always present and may be massive. In some patients splenic enlargement is associated with considerable discomfort, pain or indigestion.
- Features of anaemia may include pallor, dyspnoea and tachycardia.
- Bruising, epistaxis, menorrhagia or haemorrhage from other sites because of
abnormal platelet function. - Gout or renal impairment caused by hyperuricaemia from excessive purine breakdown may be a problem.
- Rare symptoms include visual disturbances and priapism.
Lab Diagnosis:
CBC:
- Normochromic normocytic anaemia is usual.
- Platelet count may be increased (most frequently), normal or decreased.
Leukocytosis:
- Main feature and may reach levels greater than 200× 109 /L.
- WBC are median 1,50000 (hallmark of CML).
- The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes.
- Increased circulating basophils are a characteristic feature.
Blood film:
- Circulating cells are predominantly neutrophils, metamyelocytes, myelocytes, but basophils and eosinophils are also prominent and platelets are usually increased.
Bone marrow:
- Bone marrow is hypercellular with granulopoietic predominance (increased no of granulocytic and megakaryocytic precursors.
Cytogenetic:
- Presence of the BCR‐ABL1 gene fusion by RT‐PCR analysis and in 98% of cases Ph chromosome on cytogenetic analysis.
Biochemistry:
- Serum uric acid is usually raised.
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