Chronic Leukaemias Overview

Study Notes

Chronic leukaemias can be broadly subdivided into chronic myeloid leukaemia and chronic lymphoid leukaemia.
Chronic myeloid leukaemia (CML) is the most common type of chronic leukaemia.
CML is associated with the Philadelphia chromosome.

CML is an acquired clonal disorder of pluripotent stem cells.
CML is caused by a reciprocal translocation between chromosomes 9 and 22.
This translocation moves part of the Abelson protooncogen (ABL) to the (BCR) gene on chromosome 22 and part of chromosome 22 moves to chromosome 9.
The abnormal chromosome 22 is known as the Philadelphia chromosome (Ph).
The resulting chimeric BCR-ABL gene codes for a fusion protein with tyrosine kinase activity in excess of normal.

### BCR-ABL Fusion Protein

BCR-ABL fusion proteins are either 210KDa or 190KDa in size.
The 210KDa protein results from a breakpoint in BCR that is further downstream, while the 190KDa protein results from a breakpoint that is further upstream.
Rarely, a breakpoint in μ-BCR producing a P230kda fusion protein occurs and is prominent in neutrophilic leukaemia.
In a minority of patients, the Philadelphia chromosome is not seen microscopically.

CML has a male:female ratio of 1.4:1.
CML can occur at any age, including in children and neonates.
The most common age for presentation is between 40-60.
Symptoms often relate to hypermetabolism, including weight loss, lassitude, anorexia, and night sweats.
Gout and renal impairment due to hyperuricemia may also occur.
Bone marrow failure can lead to bruising, epistaxis, menorrhagia, and hemorrhage as a result of platelet dysfunction.
Organ infiltration often results in splenomegaly, which is almost always present and frequently massive.
Rare symptoms include visual disturbance.

A complete blood count (CBC) shows:
- Normochromic normocytic anemia.
- Leucocytosis >50 x 10^9/L to >500 x 10^9/L.
- Platelet count is increased, normal, or decreased.
In a peripheral blood film, all myeloid series cells are observed with increased circulating basophils.
The bone marrow is hypercellular with myeloid hyperplasia.