Atypical CML: diagnosis and treatment

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Atypical chronic myeloid leukemia (aCML) is now classified as MDS/MPN with neutrophilia.
• aCML is characterized by granulocytic dysplasia and over 10% circulating immature myeloid cells.
• Diagnosis is morphologically based, with somatic mutations aiding but not pathognomonic.

Purpose of the Study:

• To review the current understanding of aCML, including its classification, diagnostic features, genetic landscape, and treatment strategies.
• To highlight the evolving genomic insights into aCML.
• To discuss the challenges in risk stratification and treatment consensus.

Main Methods:

• Review of current literature and classifications (ICC, WHO).
• Analysis of common and low-frequency somatic mutations in aCML.
• Examination of prognostic factors and treatment outcomes.

Main Results:

• Key mutations include ASXL1, SETBP1, NRAS, KRAS, SRSF2, and TET2; SETBP1 and ETNK1 are secondary events.
• Mayo Clinic prognostic score identifies age >67, Hb <10 g/dL, and TET2 mutations as adverse.
• Allogeneic transplant is the only curative option, despite identified genetic markers.

Conclusions:

• aCML (MDS/MPN with neutrophilia) has distinct morphologic and genetic features.
• Further research is needed for consensus on risk stratification and treatment.
• Allogeneic stem cell transplantation remains the definitive curative therapy.