Chronic Myeloid Leukemia Diagnostics

Diagnostic tests that can be done include a complete blood count (CBC) with differential and platelet count, along with a biochemical profile that encompasses hepatitis B serology, cholesterol, lipase, hemoglobin A1c, and an electrocardiogram (ECG).  

Peripheral Blood Smear (PBS)

PBS findings in CML include absolute basophilia and eosinophilia, as well as leukocytosis (approximately 100,000/µL). A classic finding in CML is the presence of mature metamyelocytes, referred to as a “leukemic hiatus” or myelocyte bulge.  

Bone Marrow Aspirate and Biopsy  

Bone marrow aspirate and biopsy are used as part of the initial workup and for the detection of other chromosomal abnormalities that cannot be detected on peripheral blood fluorescence in situ hybridization (FISH). They reveal granulocytic hyperplasia with a maturation pattern, increased reticulin fibrosis and vascularity, widened areas of immature neutrophils, decreased erythroid islands, presence of dwarf megakaryocytes, decreased iron-laden macrophages, and increased cell turnover with pseudo-Gaucher cells and sea-blue histiocytes. Morphologic review also contains the percentage of blasts and basophils.

Genetic Tests  

Cytochemistry is used to differentiate myeloid from lymphoid blasts in the blastic phase of CML. Cytogenetics was the test that initially identified the Ph chromosome using May-Grünwald-Giemsa (MGG) banded metaphase chromosomes. If both Ph and BCR::ABL1 are positive, a chronic or advanced phase of CML is confirmed; whereas if both are negative, the patient should be evaluated for other diseases. Bone marrow cytogenetics with a minimum of 20 metaphases should be done initially to detect additional chromosomal abnormalities in Ph-positive cells (ACA/Ph+) or signs of clonal cytogenetic evolution.







FISH analysis is used to identify the chromosomal positions of the BCR and ABL1 genes in metaphase chromosome preparations. It is also used in the utilization of the interphase cells from bone marrow or peripheral blood. The presence of co-localization of BCR and ABL probes indicates the presence of fused BCR::ABL1 genes. Detection of the BCR::ABL1 transcript in blood granulocytes is recommended to differentiate between de novo BP-CML and de novo Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). Quantitative reverse transcription-polymerase chain reaction (qPCR) using the International Scale involves using primers to amplify DNA fragments from the mRNA transcripts of BCR::ABL1 genes. It can detect gene fusions, including e1a2, e13a2 (b2a2), e14a2 (b3a2), and e19a2 genes. Detection of atypical BCR::ABL1 transcripts may be accomplished using dual fusion D-FISH or qualitative reverse transcription polymerase chain reaction (RT-PCR) to confirm FISH and qPCR test results. Other chromosomal abnormalities related to CML (eg trisomy 8, trisomy 19, duplication of the Ph chromosome, isochromosome 17q), are referred to as additional clonal cytogenetic aberrations (ACAs). These abnormalities are associated with poorer progression-free survival (PFS) and overall survival (OS).  

Human Leukocyte Antigen (HLA) Testing  

HLA testing is done if the patient is considered for allogeneic hematopoietic cell transplant (HCT) (allo-HCT).