Update on CML-Like Disorders.

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Chronic myeloid leukemia (CML) is typically defined by the BCR-ABL1 fusion gene.
• Historically, 'BCR-ABL1 negative CML' described a clinically diverse group with poor prognosis.
• This entity represents approximately 5% of CML cases.

Purpose of the Study:

• To clarify the classification and diagnostic considerations for BCR-ABL1 negative CML.
• To differentiate these cases from BCR-ABL1 positive CML and other myeloid neoplasms.

Main Methods:

• Review of historical literature and current diagnostic criteria for myeloid neoplasms.
• Analysis of cytogenetic and molecular findings in BCR-ABL1 negative cases.
• Differential diagnosis based on clinical heterogeneity and specific molecular markers.

Main Results:

• Most BCR-ABL1 negative CML cases are now classified as subtypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN).
• These include atypical CML (aCML), chronic myelomonocytic leukemia (CMML), and chronic neutrophilic leukemia (CNL).
• A minority are reclassified as systemic mastocytosis with associated hematological neoplasm (SM-AHN) or myeloid/lymphoid neoplasms with eosinophilia.

Conclusions:

• The term 'BCR-ABL1 negative CML' is largely outdated.
• Accurate classification relies on identifying specific molecular drivers and adhering to current MDS/MPN diagnostic guidelines.
• Proper diagnosis is crucial for appropriate patient management and prognosis.