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Editorials
changes. The assumption that this problem might easily be solved by detecting somatic mutations turned out to be a false hope. Matters were complicated by the discovery of “age-related clonal hematopoiesis”,7 also known as “clonal hematopoiesis with indeterminate potential”,8 and “clonal hematopoiesis with oncogenic potential”.9 These condi- tions are associated with well-known hemato-oncological driver mutations but do not necessarily lead to overt hema- tologic malignancy. The older the patient, the less certain we can be that detection of a somatic mutation is positive proof of malignant disease.
Against this background, an international working group of hematologists and hemotopathologists met in Vienna and developed proposals on how to tackle the diagnostic problems in the gray area between reactive monocytoses and acute leukemias with monocytosis.1
According to their suggestions, the heterogeneous group of reactive monocytoses is now complemented by “idio- pathic monocytosis of undetermined significance”, which is conceptually equivalent to idiopathic cytopenia of undeter- mined significance. The category of “idiopathic monocyto- sis of undetermined significance” includes patients with
monocytosis that is neither attributable to a plausible med- ical cause nor identifiable as a clonal proliferation.
These reactive or unclear monocytoses should be differ- entiated from clonal disorders that carry a risk of progres- sion to overt CMML or acute myeloid leukemia. Therefore, “clonal monocytosis of undetermined significance” was proposed, in order to classify a disorder that does not yet fulfill the formal criteria of CMML. Very recently, another group showed that patients with clonal monocytosis iden- tified by targeted gene sequencing have a clinical outcome similar to that of those with overt World Health Organization-defined CMML.10 Accordingly, these “not- yet-CMML” cases might also be called “clonal monocytosis of clinical significance”. The relationship between these conditions and CMML resembles that between “clonal cytopenia of undetermined significance” and MDS.11 Other clonal entities between reactive monocytosis and CMML are “RASopathies”, which can develop into juvenile myelomonocytic leukemia, as well as certain histiocytoses.
However, a clinical hematologist is more likely to encounter the three types of CMML, characterized by either a more dysplastic or a more proliferative appearance,
Figure 1. Relationship between different types of clonal monocytosis and demarcation from non-clonal, reactive monocytoses. EBV: Epstein-Barr virus; GM-CSF: granulocyte-macrophage colony-stimulating factor; IMUS: idiopathic monocytosis of undetermined significance; ICUS: idiopathic cytopenia of undetermined signifi- cance; CMUS: clonal monocytosis of undetermined significance; MDS-MLD: myelodysplastic syndrome with multilineage dysplasia; MPN-MDS: myeloproliferative neo- plasm-myelodyplastic syndrome; CMML-SM: chronic myelomonocytic leukemia with systemic mastocytosis; MDS-EB: myelodysplastic syndrome with excess blasts; JMML: juvenile myelomonocytic leukemia; AMML: acute myelomonocytic leukemia.
haematologica | 2019; 104(10)
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