The diagnosis of chronic myelogenous leukemia is confirmed via peripheral blood karyotyping or FISH showing presence of the translocation between chromosomes 9 and 22 (which causes the BCR gene to come into proximity with the ABL gene. A bone marrow biopsy can also be done to aid in the diagnosis and to better assess for Philadelphia chromosome-positive metaphases.

The diagnosis of chronic myelogenous leukemia is confirmed via one or more of the following studies done on peripheral blood:

• Conventional cytogenetics: This tests assess the presence and morphology of chromosomes in cells.^[1]
• Fluorescence in situ hybridization (FISH) analysis: This test confirms the presence of the translocation between chromosomes 9 and chromosome 22 (which causes the BCR gene to come into proximity with the ABL gene).^[1]
• Reverse transcriptase polymerase chain reaction (RT-PCR):This can be done to assess for BCR-ABL transcripts at the mRNA level. This test is more sensitive and is more commonly used in the current era when assessing response to therapy.^[1]

Peripheral blood smear may show:^[2]

• Absolute leukocytosis (median of 100,000/µL) with a left shift and classic myelocyte bulge (more myelocytes than the more mature metamyelocytes seen on the blood smear)
• Blasts usually number <2%
• Absolute basophilia, in 90% of cases
• Monocytosis is often seen, but generally not an increased monocyte percentage
• Absolute monocytosis is more prominent in the unusual cases with a p190 BCR/ABL
• Platelet count is usually normal or elevated
• Thrombocytopenia suggests an alternative diagnosis or the presence of advanced stage, rather than chronic phase disease
• Increase in myeloid cells at various stages of maturation (i.e. metamyelocytes and band forms)

The various investigations should be performed in the following order:^[2]

• Peripheral blood smear review
• Peripheral blood studies
• Bone marrow biopsy