Oligomonocytic and overt chronic myelomonocytic leukemia show similar clinical, genomic, and immunophenotypic features

Abstract

Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic syndromes (MDSs) or myelodysplastic/myeloproliferative neoplasms, unclassifiable with relative monocytosis (≥10% monocytes) and a monocyte count of 0.5 to <1 × 109/L. These patients show clinical and genomic features similar to those of overt chronic myelomonocytic leukemia (CMML), although most of them are currently categorized as MDS, according to the World Health Organization 2017 classification. We analyzed the clinicopathologic features of 40 patients with OM-CMML with well-annotated immunophenotypic and molecular data and compared them to those of 56 patients with overt CMML. We found similar clinical, morphological, and cytogenetic features. In addition, OM-CMML mirrored the well-known complex molecular profile of CMML, except for the presence of a lower percentage of RAS pathway mutations. In this regard, of the different genes assessed, only CBL was found to be mutated at a significantly lower frequency. Likewise, the OM-CMML immunophenotypic profile, assessed by the presence of >94% classical monocytes (MO1s) and CD56 and/or CD2 positivity in peripheral blood monocytes, was similar to overt CMML. The MO1 percentage >94% method showed high accuracy for predicting CMML diagnosis (sensitivity, 90.7%; specificity, 92.2%), even when considering OM-CMML as a subtype of CMML (sensitivity, 84.9%; specificity, 92.1%) in our series of 233 patients (39 OM-CMML, 54 CMML, 23 MDS, and 15 myeloproliferative neoplasms with monocytosis and 102 reactive monocytosis). These results support the consideration of OM-CMML as a distinctive subtype of CMML.

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

“…(Table 6) The first prerequisite criterion is persistent absolute (≥0.5 × 10 9 / L) and relative (≥10%) peripheral blood monocytosis. Namely, the cutoff for absolute monocytosis is lowered from 1.0 ×10 9 /L to 0.5 ×10 9 /L to incorporate cases formerly referred to as oligomonocytic CMML [45][46][47]. To enhance diagnostic accuracy when absolute monocytosis is ≥0.5 ×10 9 /L but <1.0 ×10 9 /L, detection of one of more clonal cytogenetic or molecular abnormality and documentation of dysplasia in at least one lineage are required.…”

“…45 Department of Paediatrics, University of Oxford, Oxford, UK. 46 Department of Oncology, University of Oxford, Oxford, UK. 47 Immunology Division, Garvan Institute of Medical Research, Sydney, Australia.…”

Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

“…Molecular subtypes of MDS/MPN-U displayed hematological BM and PB counts in accordance with their phenotypic group. For example, the ‘CMML-like’ group displayed increased monocyte count and included a few patients that could be classified as oligomonocytic CMML (monocyte count of 0.5 to <1 × 10 9 /L, ≥10% monocytes) [ 92 ]. Similarly, ‘MDS/MPN-RS-T-like’ patients displayed a median percentage of RS higher than the other groups and, clinically, behaved similarly to MDS/MPN-RS-T patients, suggesting that it might be worth considering taking the presence of SF3B1 mutations into account in patients with 5–15% of ring sideroblasts, as in MDS-RS.…”

Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q represents a distinct clinico-biologic subset: a multi-institutional collaborative study from the Bone Marrow Pathology Group

“…These include NPM1 mutated non-acute myeloid neoplasms, the majority of which are classified as MDS or as one of the MDS/MPN entities, although these cases are more akin to NPM1 mutated AML based on the disease biology, evolution and therapy response [ 12 , 19 ]. Oligomonocytic CMML, despite not meeting the currently proposed WHO criteria for CMML, shows a similar underlying genomic and immunophenotypic profile and outcome to CMML [ 20 – 23 ]. One study has also recognized MDS/MPN-U with ≥15% ring sideroblasts but not fulfilling the hematologic criteria for MDS/MPN-RS-T to be within the spectrum of the same disease [ 24 ].…”