Can CML Progress to AML?
Yes, CML can progress to blast phase that resembles acute leukemia, including acute myeloid leukemia (AML), though this represents disease transformation rather than development of a separate AML. 1
Understanding CML Disease Progression
CML naturally progresses through three distinct phases if left untreated or inadequately treated:
- Chronic phase (CP-CML) → Accelerated phase (AP-CML) → Blast phase (BP-CML) 1
- Without effective treatment, untreated CP-CML will progress to AP-CML or BP-CML in 3 to 5 years on average 1
- With modern tyrosine kinase inhibitor (TKI) therapy, the annual progression rate has dramatically decreased to 1-1.5% from the historical >20% 2
Blast Phase: The "AML-Like" Transformation
Blast phase CML is defined as ≥20% blasts (WHO criteria) or ≥30% blasts (International Bone Marrow Transplant Registry criteria) in blood or bone marrow 1, 2:
- 70-80% of blast phase cases are myeloid phenotype, resembling AML 1
- Approximately 30% are lymphoid phenotype 3
- Mixed phenotypes can occur 1
The key distinction is that blast phase CML remains BCR-ABL1 positive disease (Philadelphia chromosome positive), whereas de novo AML is BCR-ABL1 negative 1, 2. This is a critical difference because:
- BP-CML represents transformation of the original CML clone 1
- The genetic instability of BCR-ABL1-positive cells drives this progression through accumulation of additional mutations 1, 4
- Gene expression profiling shows the bulk of genetic changes occur during the transition from CP to AP, with AP and BP showing similar expression patterns 1
Rare Exception: True AML Development
In extremely rare cases, true BCR-ABL1-negative AML can develop in CML patients during TKI therapy 5:
- This represents a separate clonal event, not CML transformation 5
- Can occur even in patients achieving cytogenetic response to imatinib 5
- Does not require development of secondary cytogenetic abnormalities 5
Clinical Implications and Prognosis
Survival in blast phase is generally less than 1 year without successful intervention 6, 7:
- Blast phase CML responds poorly to standard AML chemotherapy compared to de novo AML 2
- Allogeneic stem cell transplantation is considered the only curative therapy for BP-CML 6, 3
- Early indicators of progression include additional chromosomal aberrations, somatic mutations, and clinical deterioration 6
Monitoring to Prevent Progression
Regular monitoring with quantitative PCR for BCR-ABL1 transcripts every 3 months is essential 6, 2:
- Early molecular response milestones: BCR-ABL1 ≤10% at 3 months and ≤1% at 12 months 2
- Bone marrow examination should be performed if progression is suspected to determine CML phase 6
- BCR-ABL1 kinase domain mutation analysis guides selection of subsequent TKI therapy if resistance develops 6
Common pitfall: Confusing blast phase CML (which is BCR-ABL1 positive) with de novo AML (which is BCR-ABL1 negative). Always confirm Philadelphia chromosome/BCR-ABL1 status, as this fundamentally changes treatment approach and prognosis 1, 2.