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Chronic myeloid leukemia

15 min

Skills you'll build3 skills
  • Recognize a broad myeloid maturation spectrum in a CML-compatible pattern
  • Identify the genetic finding that establishes CML
  • Assign a CML phase from blast and basophil percentages under WHO5 or ICC

At the bench: Recognize abnormal cell findings that need further review

Try first

Try first

A film shows marked neutrophilic leukocytosis with granulocytes present at every stage of maturation, most of them myelocytes and segmented neutrophils, along with basophilia. Blasts are 1%. How do you describe this pattern?

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

The maturation spectrum

Chronic-phase CML commonly produces marked neutrophilic leukocytosis with granulocytes present at every stage of maturation, most of them myelocytes and segmented neutrophils, together with basophilia and sometimes eosinophilia.1 Platelets can be increased, and the marrow is hypercellular with granulocytic proliferation and small hypolobated megakaryocytes.1 Blast phase requires at least 20% myeloid blasts in blood or marrow, an extramedullary blast proliferation, or increased lymphoblasts in blood or marrow.1,2 A broad spectrum with few blasts and prominent basophilia is well below that threshold. Calling it blast-rich reports a phase the film does not show. On a later film, a rising blast count must be reported, because it can signal blast phase.

Establishing CML

A film like this raises suspicion for CML, and a leukemoid reaction from infection or another reactive cause can look similar. CML is established by detecting BCR::ABL1. Karyotype, fluorescence in situ hybridization (FISH), or reverse-transcription PCR (RT-PCR) can each confirm the fusion, and a visible t(9;22) translocation is not required, because cryptic and variant rearrangements occur.1,3 Baseline RT-PCR also identifies the transcript, because the later monitoring assay must target the same one.3 Marrow morphology and karyotyping then assess phase and any additional chromosomal abnormalities.1

Assigning a phase

WHO5 keeps only chronic phase and blast phase. It treats 10% to 19% blasts, basophils of 20% or more, additional clonal abnormalities, or treatment resistance as high-risk chronic-phase findings.1,4 ICC keeps a separate accelerated-phase category at those same levels.2 Both frameworks place blast phase at 20% or more myeloid blasts in blood or marrow, or an extramedullary blast proliferation, and both treat a rising lymphoblast count as urgent even below that cutoff, because the lymphoblast threshold for blast phase is not established.1,2 State the framework applied in the report, because the two frameworks give the same findings different phase names.

Follow the bench demonstration

Sources for this step
References
  1. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703-1719. doi:10.1038/s41375-022-01613-1
  2. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228. doi:10.1182/blood.2022015850
  3. Cross NCP, Ernst T, Branford S, et al. European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia. Leukemia. 2023;37(11):2150-2167. doi:10.1038/s41375-023-02048-y
  4. Apperley JF, Milojkovic D, Cross NCP, et al. 2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Leukemia. 2025;39(8):1797-1813. doi:10.1038/s41375-025-02664-w

Watch one

Read each decision and its explanation.

A CBC shows WBC 68 × 10³/µL with granulocytes present at every stage of maturation, most of them myelocytes and segmented neutrophils. Basophils are 4% and blasts are 1%. Platelets are 520 × 10³/µL. What do you do next?

  1. Check the blast percentage. At 1% it is far below the 20% that defines blast phase.

    The blast percentage determines whether an acute process is the immediate concern.

  2. Review the whole spectrum. Granulocytes appear at every maturation stage, most at the myelocyte and segmented neutrophil stages, with basophilia. This fits the chronic-phase CML pattern.

    The breadth of the spectrum together with basophilia is the pattern that raises suspicion for CML.

  3. Refer the specimen for BCR::ABL1 testing by karyotype, FISH, or RT-PCR, because a visible t(9;22) is not required to confirm the fusion.

    Film findings alone cannot establish the disease.

  4. Request baseline RT-PCR to identify the transcript type at the same time as diagnostic testing.

    The monitoring assay used later must target the same transcript identified now.

Assign the phase after the marrow studies and the genetic result are back. The phase requires the marrow blast and basophil percentages and the confirmed fusion.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A new chronic myeloid leukemia (CML) diagnosis is confirmed by chromosome banding and fluorescence in situ hybridization (FISH). Why is reverse-transcription PCR still required at diagnosis?

Incorrect. FISH and banding already show the genomic rearrangement. DNA methods do not identify the expressed transcript.

Incorrect. Banding and FISH showing the BCR::ABL1 rearrangement already establish the genetic finding. PCR adds the transcript type, which DNA FISH cannot identify.

Correct. DNA FISH shows the rearrangement. It does not show the expressed transcript. The common e13a2 and e14a2 transcripts are reported on the BCR::ABL1 International Scale, and an atypical transcript needs a validated personalized assay reported against the patient's baseline.

Hint
  1. Chromosome banding and FISH already show the rearrangement.
  2. A DNA-level result and an RNA-level result give different information.
  3. The later monitoring assay targets one specific transcript.

Review Recurrent abnormalities

Problem 2 of 3 · Hints available

A new chronic myeloid leukemia (CML) diagnosis shows 15% blasts and 22% basophils in blood, with 12% blasts in marrow and no extramedullary disease. How is this pattern classified under WHO5?

Incorrect. Blast phase requires at least 20% myeloid blasts in blood or marrow, an extramedullary blast proliferation, or increased lymphoblasts in blood or marrow.

Correct. WHO5 omits the accelerated phase and treats 10% to 19% blasts and basophils of 20% or more as high-risk chronic-phase features. ICC would call the same pattern accelerated phase, so the report names its framework.

Incorrect. WHO5 has no formal accelerated phase. ICC keeps one, and under ICC this pattern would qualify.

Hint
  1. Compare the blast percentage with the 20% blast-phase threshold first.
  2. WHO5 and ICC treat 10% to 19% blasts differently.
  3. Name the framework that matches the phase term used.

Review Chronic myeloid leukemia

Problem 3 of 3 · On your own

A different film shows WBC 92 × 10³/µL with granulocytes at every maturation stage, most segmented neutrophils and myelocytes. Basophils are 6% and blasts are 3% in blood, 4% in marrow. No extramedullary disease is reported. How do you describe this pattern?

Blast phase requires at least 20% myeloid blasts in blood or marrow. Blasts of 3% and 4% are far below that, at any basophil percentage.

Called a broad maturation spectrum blast-rich

Chronic-phase CML shows granulocytes at every stage of maturation, with most at the myelocyte and segmented neutrophil stages, plus basophilia and few blasts. At least 20% myeloid blasts in blood or marrow defines blast phase. Calling a maturation spectrum blast-rich reports a blast phase that is absent, and overlooking a rising blast count misses a real one.

Granulocytes at every maturation stage with few blasts is the broad spectrum of chronic-phase CML. Blasts of 3% and 4% and basophils of 6% are below the WHO5 high-risk levels of 10% blasts and 20% basophils.

A left shift this broad, spanning every maturation stage with basophilia this high, exceeds what a reactive process typically produces.

Review Chronic myeloid leukemia

Use it

Use the specimen and readings to make the next bench decision. The step is complete without it.

Try this at the MicroscopeWBC0 / 100MANUAL DIFF ORDEREDPeripheral blood differentialPerform manual diff

For reference

Sources checked