Atypical chronic myeloid leukemia (aCML)
- Method:
- Anticoagulant:
- Recommendation:
- Method:Cytomorphology
- Anticoagulant:EDTA
- Recommendation:obligatory
- Method:Immunophenotyping
- Anticoagulant:EDTA or Heparin
- Recommendation:facultative
- Method:Chromosome analysis
- Anticoagulant:Heparin
- Recommendation:obligatory
- Method:FISH
- Anticoagulant:
- Recommendation:no
- Method:Molecular genetics
- Anticoagulant:EDTA or Heparin
- Recommendation:obligatory
Based on the current guidelines and the current state of research, there are different diagnostic recommendations for patients with atypical chronic myeloid leukemia. We have summarized the most important information on classification and diagnostic methods at the MLL for you.
aCML: Classification
According to the 2017 WHO classification, aCML, BCR::ABL1-negative is categorized as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) (Swerdlow et al. 2017).
Diagnostic criteria:
- Peripheral blood (PB) leukocytosis (≥ 13 x109/L), due to increased numbers of neutrophils and their precursors, with neutrophil precursors constituting ≥ 10% of the leukocytes
- Dysgranulopoiesis
- No or minimal basophilia (basophils < 2% of leukocytes in PB)
- No or minimal monocytosis (monocytes < 10% of leukocytes in PB)
- Hypercellular bone marrow with granulocytic proliferation and dysplasia; with or without dysplasia in the erythroid and megakaryocytic lineages
- < 20% blasts in PB and bone marrow
- Exclusion of a PDGFRA, PDGFRB or FGFR1 rearrangement as well as a PCM1::JAK2 rearrangement
- Exclusion of a BCR::ABL1-positive CML, PMF, PV or ET
aCML: Diagnostic methods and their relevance
Cytomorphology is used for differentiation from other myeloproliferative disorders (MPN), CMML and myelodysplastic syndrome (MDS) and for securing the diagnosis. It is also required for classification according to WHO.
Chromosomal alterations have been detected in approximately 40-80% of patients with aCML (Swerdlow et al. 2017, Meggendorfer et al. 2018). The abnormalities known from MPN and MDS occur. Most frequently, gain of a chromosome 8 was observed. Aberrations of chromosomes 7, 12, 13, 14, 17, 19, and 20 and a complex karyotype have also been described (Wang et al. 2014, Swerdlow et al. 2017).
Molecular genetics can be used to detect common mutations in aCML, which are summarized in Figure 1. While ASXL1, TET2, and SRSF2 are the most frequently mutated but also occur nonspecifically in other myelodysplastic/myeloproliferative neoplasms, SETBP1, ETNK1, and CBL mutations show a more frequent occurrence in aCML compared to other neoplasms. Of the known aberrations, ASXL1 and SETBP1 are of prognostically unfavorable relevance (Meggendorfer et al. 2013, Piazza et al. 2013, Zoi & Cross 2015, Meggendorfer et al. 2018). For differential diagnostics, chronic neutrophil leukemia (CNL) should be considered when CSF3R is mutated. In addition, mutations in CSF3R and JAK2 allow specific therapy.
aCML: Prognosis
A leukocyte count of >50x109/L has been described as a prognostically negative parameter in aCML in several studies (Onida et al. 2002, Breccia et al. 2006, Wang et al. 2014). In some of these studies, age >65 years, female gender and hemoglobin level <10 g/dL were also prognostically unfavorable. In addition, a SETBP1 mutation was shown to have a negative impact (Piazza et al. 2013). 30-40% of patients with aCML show transformation into AML (Wang et al. 2014).
aCML: Recommendation
It should be noted that according to WHO 2017, when a CSF3R mutation is detected, CNL should be excluded morphologically as part of the differential diagnoses. Similarly, if a JAK2, CALR, or MPL mutation is detected, an accelerated phase of MPN should be excluded based on history.
In contrast, according to WHO 2017, the presence of a SETBP1 or ETNK1 mutation supports the diagnosis of atypical CML.
Status: June 2022