Chronic myeloid leukaemia (CML), also known as chronic granulocytic leukaemia and chronic myelogenous leukaemia, is a chronic myeloproliferative neoplasm that results from a t(9;22)(q34;q11.2) translocation occurring in a pluripotent lymphoid-myeloid haemopoietic stem cell. The translocation gives rise to an abbreviated chromosome 22 (22q-) referred to as the Philadelphia (Ph) chromosome. It also leads to formation of a BCR-ABL1 fusion gene that encodes a constitutively activated tyrosine kinase.
CML is a biphasic or triphasic disease. Following a chronic phase of variable length, there is transformation to acute leukaemia ('blast transformation') that is usually myeloid but sometimes lymphoblastic or mixed lineage. An accelerated phase can precede acute transformation. Some patients present in acute transformation without a clinically apparent chronic phase. Aetiological factors include irradiation  and probably exposure to topoisomerase-II-interactive drugs .
Some patients are diagnosed as a result of an incidental blood count. Others have symptoms such as fatigue, lethargy, weight loss, abdominal discomfort and early satiety. Physical examination may show splenomegaly and less often hepatomegaly.
During the accelerated phase there may be refractory splenomegaly. Acute transformation is characterized by variable combinations of pallor, bruising and bleeding, lymphadenopathy, soft tissue or bone infiltration and increasing splenomegaly.
Haematological and pathological features
The blood count shows leucocytosis and anaemia. The majority of patients have a normal platelet count or thrombocytosis but a minority have thrombocytopenia. The leucocytosis is the result of a generalized increased in myeloid cells  (Figures 4.1 and 4.2). There is neutrophilia, basophilia and often eosinophilia. Granulocyte precursors are also present in the blood but orderly differentiation is preserved so that blast cells are less numerous than promyelocytes, which in turn are less numerous than myelocytes. The two most numerous cells in the differential count are myelocytes and mature neutrophils. Prominent monocytosis is rarely present and is associated with a BCR-ABL1 fusion gene encoding a p190 protein rather than the p210 protein more usually seen in CML. The anaemia is mild to moderate with normocytic normochromic red cells. Patients who present with thrombocytosis with little or no elevation of the white cell count and who are found to have a BCR-ABL1 fusion gene should be regarded as having a variant form of CML.
Peripheral blood film of a patient with CML showing neutrophils and their precursors, one basophil and one eosinophil precursor. MGG, high power.
Peripheral blood film of a patient with CML showing granulocytes (neutrophils, eosinophils and a basophil) and their precursors. MGG, high power.
During the accelerated phase there may be worsening anaemia (with anisocytosis and poikilocytosis), thrombocytopenia, increasing blast cells and increasing numbers ...