Chronic myelomonocytic leukemia

Résumé 0

Chronic myelomonocytic leukemia (CMML) is classified by the World Health Organization as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Observed mostly in aging people, this chronic myeloid malignancy is characterized by the expansion of CD14+,CD16- classical monocytes expressing pro-inflammatory genes. In most cases, granulocytes also expand, since some of them are endowed with immunosuppressive properties. The disease is driven by the accumulation of somatic variants in epigenetic, splicing, and signaling genes in the stem cell compartment, and by epigenetic reprogramming. As a consequence of abnormal DNA methylation, the repartition of circulating monocyte subsets is altered. Flow cytometry is used to detect an increase in the fraction of classical CD14+CD16- monocytes (>94%) or a decrease in the fraction of non-classical CD14low,CD16+,Slan+ monocytes (1.7%) among total circulating monocytes. In some patients, mature cells of the leukemic clone include plasmacytoid dendritic cells, which form islands in the bone marrow, or mastocytes, which infiltrate the skin or expand within other tissues. Cytokines and chemokines released by leukemic cells contribute to the creation of an inflammatory climate which either promotes the expansion of the leukemic clone or reduces the growth of wild-type cells. The suspected role of other components of the bone marrow niche in driving CMML emergence and progression remains poorly understood. The clinical expression of the disease is highly variable, and the accumulation of symptoms over time eventually leads to physical exhaustion and patient death as a consequence of cytopenia, acute leukemic transformation, and comorbidities. Fifty years after its identification, CMML remains one of the most severe chronic myeloid malignancies for which allogeneic stem cell transplantation is the only disease-modifying therapy. The proliferative component of the disease merits specific therapeutic approaches, distinct from those explored in myelodysplastic neoplasms. The present review emphasizes CMML specificities and discusses how this disease could benefit from dedicated therapies.