Why CML is Classified as a Myeloproliferative Neoplasm While AML is Not
The fundamental distinction lies in blast percentage and disease biology: CML is characterized by effective maturation of myeloid cells with <20% blasts and chronic proliferation driven by the BCR-ABL1 fusion gene, whereas AML is defined by ≥20% blasts representing a maturation arrest, making it an acute leukemia rather than a chronic myeloproliferative process. 1, 2
The Critical Blast Threshold
The WHO classification establishes a clear demarcation based on blast percentage that fundamentally separates these entities:
AML requires ≥20% blasts in peripheral blood or bone marrow (with specific exceptions for certain genetic abnormalities like t(8;21), inv(16), and t(15;17) where the genetic abnormality alone suffices for diagnosis regardless of blast count) 2
CML maintains <10% blasts in chronic phase (the phase in which ~90% of patients present), with effective maturation of granulocytes through all stages of development 3
When CML progresses to ≥20% blasts, it transforms into CML blast phase (CML-BP) and is no longer considered a myeloproliferative neoplasm in its pure form but rather an acute leukemic transformation 3
Disease Biology and Maturation Patterns
The classification reflects fundamentally different biological processes:
CML as a Myeloproliferative Neoplasm:
- Characterized by dysregulated but effective myeloid maturation, with increased production of mature and maturing granulocytes, mainly neutrophils 4, 3
- Driven by the BCR-ABL1 fusion gene creating constitutively active tyrosine kinase signaling that promotes proliferation while preserving differentiation capacity 3, 5
- Presents with chronic, indolent course in 90% of cases with preserved cell maturation 3
AML as an Acute Leukemia:
- Characterized by maturation arrest with accumulation of immature blasts that fail to differentiate into functional mature cells 2
- Driven by diverse genetic abnormalities affecting differentiation pathways, not primarily proliferation with preserved maturation 2
- Presents acutely with rapid accumulation of non-functional blasts 2
The Nomenclature Evolution
The WHO classification deliberately changed terminology from "myeloproliferative disorders" to "myeloproliferative neoplasms" in 2008 to emphasize the clonal, neoplastic nature of these conditions while maintaining the distinction from acute leukemias 1
Key point: The term "myeloproliferative" specifically refers to chronic proliferation of relatively mature myeloid cells with preserved differentiation capacity, not simply any proliferation of myeloid lineage cells 1
The MDS/MPN Overlap Category
The WHO classification also recognizes intermediate entities that blur these boundaries:
- Chronic myelomonocytic leukemia (CMML) is classified as MDS/MPN overlap because it has both dysplastic and proliferative features, with blast counts <20% 1, 6, 7
- CMML transforms to AML when blasts reach ≥20%, at which point it is no longer classified as MDS/MPN 1, 6
Clinical Implications of This Distinction
This classification has profound therapeutic implications:
- CML is treated with tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 fusion protein, achieving survival rates similar to age-matched general population 3
- AML requires intensive cytotoxic chemotherapy or hypomethylating agents, with fundamentally different treatment goals and outcomes 1, 2
- AML evolving from MDS (AML-MDS) is often more resistant to standard chemotherapy than de novo AML, emphasizing that the biological context matters beyond just blast percentage 1
Common Pitfall to Avoid
Do not confuse "myeloid proliferation" with "myeloproliferative neoplasm": The former simply describes increased myeloid cell numbers (which occurs in both CML and AML), while the latter is a specific WHO classification category requiring chronic proliferation with preserved maturation and <20% blasts 1, 3