Abstract
Chronic myelomonocytic leukemia (CMML) was named 50 years ago to describe a myeloid malignancy whose onset is typically insidious. This disease is now classified by the World Health Organisation as a myelodysplastic syndrome (MDS)-myeloproliferative neoplasm (MPN) overlap disease. Observed mostly in ageing people, CMML is characterized by the expansion of monocytes and, in many cases, granulocytes. Abnormal repartition of circulating monocyte subsets, as identified by flow cytometry, facilitates disease recognition. CMML is driven by the accumulation, in the stem cell compartment, of somatic variants in epigenetic, splicing and signaling genes, leading to epigenetic reprogramming. Mature cells of the leukemic clone contribute to creating an inflammatory climate through the release of cytokines and chemokines. The suspected role of the bone marrow niche in driving CMML emergence and progression remains to be deciphered. The clinical expression of the disease is highly diverse. Time-dependent accumulation of symptoms eventually leads to patient death as a consequence of physical exhaustion, multiple cytopenias and acute leukemia transformation. Fifty years after its identification, CMML remains one of the most severe chronic myeloid malignancies, without disease-modifying therapy. The proliferative component of the disease that distinguishes CMML from severe MDS has been mostly neglected. This review summarizes the progresses made in disease understanding since its recognition and argues for more CMML-dedicated clinical trials.
Highlights
Flow cytometry does not detect the abnormal monocyte subset repartition observed in the peripheral blood but identifies other populations of the leukemic clones such as plasmacytoid dendritic cells whose presence informs on disease outcome
We observed that 45% of those in which flow analysis of monocyte subset repartition detects an increase of classical monocyte fraction over 94% of total monocytes (a “Chronic myelomonocytic leukemia (CMML)-like” phenotype) will demonstrate a monocytosis ≥1 × 109 /L one year later [46]
The high prevalence of mutations in genes encoding epigenome-modifying enzymes such as TET2 that is responsible for DNA demethylation [79,80,81,82] and ASXL1 that is involved in histone-modifying complexes [83] may drive the aberrant epigenetic changes observed in CMML [84,85,86,87,88]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In addition to generating increasing weakness and fatigue, the resulting insidious inflammatory climate creates deleterious cross-talks between mature and immature cells of the clone, probably affecting bone marrow niche cells This climate promotes clonal evolution at the expanse of wild-type hematopoiesis, eventually leading to patient death as a consequence of physical exhaustion, multiple cytopenias, and acute leukemia transformation. A chronic leukemia, mostly sis observed and granulocytosis with an insidious clinical onset and a relatively benign in elderly patients, had been previously associated with refractorycourse, anemiaatand least when compared acute myelomonocytic [1,2]. In 1982, the French–American–British (FAB) co-operative group included CMML as feature was an absolute monocytosis over 1 × 109/L, which was often associated with an one of five newly defined myelodysplastic syndromes (MDS) [10] (Figure 1). The WHO report emphasizes a precise morphologic evaluation to distinguish promonocytes from dysplastic monocytes and includes them into the blast cell count. In a distant and still hypothetical future, disease recognition could include epigenetic markers and niche component alterations whose characterization is still in its infancy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
