CML is most common between the ages of 20 and 50 and is rare in childhood. It comprises about 20% of all leukemias. There is an increased (total) peripheral WBC count in more than 95% of patients, with about 70% more than 50,000/mm3 (50 Ч 109/L) and about 45% more than 100,000/mm3. There is usually a predominance of myeloid cells having intermediate degrees of maturity, such as the myelocyte and early metamyelocyte. In fact, the peripheral blood smear often looks like a bone marrow aspirate. Anemia is usually present, although initially it is often slight. Later, anemia becomes moderate. There may be mild reticulocytosis with polychromatophilia, and occasionally there are a few nucleated RBCs in the peripheral blood. Platelets are normal in about 75% of patients and increased in the remainder, with about 8% having thrombocytosis more than 1,000,000/ mm3. Average patient survival is 2-4 years after onset. Terminally, 70%-80% of patients develop a picture of acute leukemia (the blast crisis); about 70% of these are AML and about 30% are ALL or rarely some other type.

Bone marrow aspiration in CML shows a markedly hypercellular marrow due to the granulocytes, with intermediate degrees of immaturity. In this respect it resembles the peripheral blood picture. Some patients develop varying degrees of marrow fibrosis and can therefore simulate myelofibrosis (myeloid metaplasia, discussed later).

On physical examination there are varying degrees of adenopathy and organomegaly. The spleen is often greatly enlarged, and the liver may be moderately enlarged. Lymph nodes are often easily palpable but generally are only slightly to moderately increased in size.

Many patients with CML have an increased number of basophils in the peripheral blood. The reason for the basophilia is not known.

An interesting aspect of CML is the presence of a specific chromosome abnormality called the Philadelphia chromosome in the leukemic cells of most patients. No other neoplasm thus far has such a consistent cytogenetic abnormality. The abnormality involves the breaking off of a portion of the long arm of chromosome number 22 (formerly thought to be number 21) of the 21-22 group in the Denver classification (G group by letter classification); the broken-off chromosome segment is usually translocated to chromosome number 9. The abnormal chromosome 22 (Philadelphia chromosome) using standard cytogenetic methods is found in approximately 85%-90% of patients with CML (reported range, 60%-95%). Those not having it seem as a group to have a worse prognosis. Interestingly, the Philadelphia chromosome has also been reported in about 25% of patients with adult-onset ALL and in some patients with the ALL variant of CML blast crisis.

Philadelphia chromosome detection usually involves cytogenetic chromosome analysis, that is, separating the chromosomes from several body cells and visually inspecting each chromosome for abnormality. It is now possible to use the nucleic acid probe (see “DNA Probe,” Chapter 14) technique for the same purpose. There is a gene area called bcr (breakpoint cluster region) in chromosome 22 that develops a crack or fissure to which a genetic area called c-abl (located at one end of the long arm of chromosome 9) becomes attached and fused. The restructured chromosome 22 with the grafted DNA material from chromosome 9 now has a hybrid gene bcr-abl at the fusion area. There is some evidence that this abnormal hybrid gene may have a role in the events that lead to the development of CML (therefore it acts as an oncogene). A DNA probe has been constructed to detect the new hybrid gene; this has been called by some “bcr gene rearrangement assay.” The DNA probe method has certain advantages over the cytogenetic method. The DNA probe can be used on peripheral blood specimens, does not require bone marrow, does not need dividing cells, and analyzes thousands of cells—versus less than 20 by cytogenetic analysis. In addition, the DNA probe is claimed to be 5%-10% more sensitive than cytogenetic analysis. At present, the bcr rearrangement assay is mostly available in reference laboratories or university medical centers.