Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Atypical Chronic Myeloid Leukemia (aCML) [C92.20]

OMIM numbers: 608232, 612990 (ASXL1), 165360 (CBL), 138971 (CSF3R), 190070 (KRAS), 164790 (NRAS), 611060 (SETBP1)

Dipl.-Ing. (FH) Tanja Hinrichsen

Scientific Background

Atypical chronic myeloid leukemia (aCML) is a leukemic disease with myelodysplastic and myeloproliferative characteristics at the time of diagnosis, and with 1-2 cases per 100 BCR/ABL1 positive chronic myeloid leukemia (CML) cases, is rare.

It is characterized by leukocytosis due to an increase in morphologically dysplastic neutrophils and precursors and is associated with unfavorable disease progression. 

Whilst a Philadelphia chromosome or BCR/ABL1 fusion gene and rearrangements of PDGFRa and PDGFRb must be excluded, chromosomal changes are found in approximately 80% of patients such as +8, Del (20q); changes in chromosomes 17, 19 and 12 are also seen.

Approximately 60% of aCML patients have mutations in ASXL1, and mutations in CBL can be detected in about 10% of patients. In the region of 30% of aCML patients have mutations in SETBP1 which can be associated with -7 and i(17)(q10) as well as mutations in ASXL1 and CBL. The presence of mutations in these genes suggests unfavorable prognosis. In addition, mutations in KRAS and NRAS are found in about 30% of patients.

Mutations in CSF3R are rare and can be used to define limits for chronic neutrophilic leukemia (CNL).